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| A self-assembly pathway to aligned monodomain gels.
July 14, 2010 at 7:35 AM
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| | A self-assembly pathway to aligned monodomain gels. Nat Mater. 2010 Jul;9(7):594-601 Authors: Zhang S, Greenfield MA, Mata A, Palmer LC, Bitton R, Mantei JR, Aparicio C, de la Cruz MO, Stupp SI Aggregates of charged amphiphilic molecules have been found to access a structure at elevated temperature that templates alignment of supramolecular fibrils over macroscopic scales. The thermal pathway leads to a lamellar plaque structure with fibrous texture that breaks on cooling into large arrays of aligned nanoscale fibres and forms a strongly birefringent liquid. By manually dragging this liquid crystal from a pipette onto salty media, it is possible to extend this alignment over centimetres in noodle-shaped viscoelastic strings. Using this approach, the solution of supramolecular filaments can be mixed with cells at physiological temperatures to form monodomain gels of aligned cells and filaments. The nature of the self-assembly process and its biocompatibility would allow formation of cellular wires in situ that have any length and customized peptide compositions for use in biological applications. PMID: 20543836 [PubMed - indexed for MEDLINE] | | |
| The visualisation of vitreous using surface modified poly(lactic-co-glycolic acid) microparticles.
July 14, 2010 at 7:35 AM
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| | The visualisation of vitreous using surface modified poly(lactic-co-glycolic acid) microparticles. Br J Ophthalmol. 2010 May;94(5):648-53 Authors: Chau DY, Tint NL, Collighan RJ, Griffin M, Dua HS, Shakesheff KM, Rose FR AIMS To demonstrate the potential use of in vitro poly(lactic-co-glycolic acid) (PLGA) microparticles in comparison with triamcinolone suspension to aid visualisation of vitreous during anterior and posterior vitrectomy. METHODS PLGA microparticles (diameter 10-60 microm) were fabricated using single and/or double emulsion technique(s) and used untreated or following the surface adsorption of a protein (transglutaminase). Particle size, shape, morphology and surface topography were assessed using scanning electron microscopy (SEM) and compared with a standard triamcinolone suspension. The efficacy of these microparticles to enhance visualisation of vitreous against the triamcinolone suspension was assessed using an in vitro set-up exploiting porcine vitreous. RESULTS Unmodified PLGA microparticles failed to adequately adhere to porcine vitreous and were readily washed out by irrigation. In contrast, modified transglutaminase-coated PLGA microparticles demonstrated a significant improvement in adhesiveness and were comparable to a triamcinolone suspension in their ability to enhance the visualisation of vitreous. This adhesive behaviour also demonstrated selectivity by not binding to the corneal endothelium. CONCLUSION The use of transglutaminase-modified biodegradable PLGA microparticles represents a novel method of visualising vitreous and aiding vitrectomy. This method may provide a distinct alternative for the visualisation of vitreous whilst eliminating the pharmacological effects of triamcinolone acetonide suspension. PMID: 20447968 [PubMed - indexed for MEDLINE] | | |
| [Repair of calvarial defects with human umbilical cord blood derived mesenchymal stem cells and demineralized bone matrix in athymic rats]
July 14, 2010 at 7:35 AM
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| | [Repair of calvarial defects with human umbilical cord blood derived mesenchymal stem cells and demineralized bone matrix in athymic rats] Zhonghua Zheng Xing Wai Ke Za Zhi. 2010 Jan;26(1):34-8 Authors: Liu GP, Li YL, Sun J, Cui L, Zhang WJ, Cao YL OBJECTIVE: To investigate the feasibility of using human umbilical cord blood derived mesenchymal stem cells (UCB-MSCs) and demineralized bone matrix (DBM) scaffolds to repair critical-sized calvarial defects in athymic rats. METHODS: Human UCB-MSCs were isolated, expanded and osteogenically induced in vitro. Osteogenic differentiation of UCB-MSCs was evaluated by Alizarin Red staining and measurement of calcium content respectively, and then the cells were seeded onto DBM scaffolds. Bilateral full-thickness defects (5 mm in diameter) of parietal bone were created in an athymic rat model. The defects were either repaired with UCB-MSC/DBM constructs (experimental group) or with DBM scaffolds alone (control group). Animals were harvested at 6 and 12 weeks post-implantation respectively, and defect repair was evaluated with gross observation, micro-CT measurement and histological analysis. RESULTS: Micro-CT showed that new bone was formed in the experimental group at 6 weeks post-implantation, while no sign of new bone formation was observed in the control group. At 12 weeks post-transplantation, scaffolds had been degraded almost completely in both sides. It was shown that an average of (78.19 +/- 6.45)% of each defect volume had been repaired in experimental side; while in the control side, only limited bone formed at the periphery of the defect. Histological examination revealed that the defect was repaired by trabecular bone tissue in experimental side at 12 weeks, while only fibrous connection was observed in the control group. CONCLUSIONS: Tissue-engineered bone composed of osteogenically-induced human UCB-MSCs on DBM scaffolds could successfully repair the critical-sized calvarial defects in athymic rat models. PMID: 20432924 [PubMed - indexed for MEDLINE] | | |
| Therapeutic angiogenesis by implantation of a capillary structure constituted of human adipose tissue microvascular endothelial cells.
July 14, 2010 at 7:35 AM
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| | Therapeutic angiogenesis by implantation of a capillary structure constituted of human adipose tissue microvascular endothelial cells. Arterioscler Thromb Vasc Biol. 2010 Jul;30(7):1300-6 Authors: Yoshida T, Komaki M, Hattori H, Negishi J, Kishida A, Morita I, Abe M OBJECTIVE: We previously reported a novel technology for the engineering of a capillary network using an optical lithographic technique. To apply this technology to the therapy of ischemic diseases, we tested human omental microvascular endothelial cells (HOMECs) as an autologous cell source and decellularized human amniotic membranes (DC-AMs) as a pathogen-free and low immunogenic transplantation scaffold. METHODS AND RESULTS: Human umbilical vein endothelial cells were aligned on a patterned glass substrate and formed a capillary structure when transferred onto an amniotic membrane (AM). In contrast, HOMECs were scattered and did not form a capillary structure on AMs. Treatment of HOMECs with sphingosine 1-phosphate (S1P) inhibited HOMEC migration and enabled HOMEC formation of a capillary structure on AMs. Using quantitative RT-PCR and Western blot analyses, we demonstrated that the main S1P receptor in HOMECs is S1P(2), which is lacking in human umbilical vein endothelial cells, and that inhibition of cell migration by S1P is mediated through an S1P(2)-Rho-Rho-associated kinase signaling pathway. Implantation of capillaries engineered on DC-AMs into a hindlimb ischemic nude mouse model significantly increased blood perfusion compared with controls. CONCLUSIONS: A capillary network consisting of HOMECs on DC-AMs can be engineered ex vivo using printing technology and S1P treatment. This method for regeneration of a capillary network may have therapeutic potential for ischemic diseases. PMID: 20431071 [PubMed - indexed for MEDLINE] | | |
| Endothelial progenitors encapsulated in bioartificial niches are insulated from systemic cytotoxicity and are angiogenesis competent.
July 14, 2010 at 7:35 AM
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| | Endothelial progenitors encapsulated in bioartificial niches are insulated from systemic cytotoxicity and are angiogenesis competent. Am J Physiol Renal Physiol. 2010 Jul;299(1):F178-86 Authors: Ratliff BB, Ghaly T, Brudnicki P, Yasuda K, Rajdev M, Bank M, Mares J, Hatzopoulos AK, Goligorsky MS Intrinsic stem cells (SC) participate in tissue remodeling and regeneration in various diseases and following toxic insults. Failure of tissue regeneration is in part attributed to lack of SC protection from toxic stress of noxious stimuli, thus prompting intense research efforts to develop strategies for SC protection and functional preservation for in vivo delivery. One strategy is creation of artificial SC niches in an attempt to mimic the requirements of endogenous SC niches by generating scaffolds with properties of extracellular matrix. Here, we investigated the use of hyaluronic acid (HA) hydrogels as an artificial SC niche and examined regenerative capabilities of encapsulated embryonic endothelial progenitor cells (eEPC) in three different in vivo models. Hydrogel-encapsulated eEPC demonstrated improved resistance to toxic insult (adriamycin) in vitro, thus prompting in vivo studies. Implantation of HA hydrogels containing eEPC to mice with adriamycin nephropathy or renal ischemia resulted in eEPC mobilization to injured kidneys (and to a lesser extent to the spleen) and improvement of renal function, which was equal or superior to adoptively transferred EPC by intravenous infusion. In mice with hindlimb ischemia, EPC encapsulated in HA hydrogels dramatically accelerated the recovery of collateral circulation with the efficacy superior to intravenous infusion of EPC. In conclusion, HA hydrogels protect eEPC against adriamycin cytotoxicity and implantation of eEPC encapsulated in HA hydrogels supports renal regeneration in ischemic and cytotoxic (adriamycin) nephropathy and neovascularization of ischemic hindlimb, thus establishing their functional competence and superior capabilities to deliver stem cells stored in and released from this bioartificial niche. PMID: 20410213 [PubMed - indexed for MEDLINE] | | |
| Functional repair of human donor lungs by IL-10 gene therapy.
July 14, 2010 at 7:35 AM
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| | Functional repair of human donor lungs by IL-10 gene therapy. Sci Transl Med. 2009 Oct 28;1(4):4ra9 Authors: Cypel M, Liu M, Rubacha M, Yeung JC, Hirayama S, Anraku M, Sato M, Medin J, Davidson BL, de Perrot M, Waddell TK, Slutsky AS, Keshavjee S More than 80% of potential donor lungs are injured during brain death of the donor and from complications experienced in the intensive care unit, and therefore cannot be used for transplantation. These lungs show inflammation and disruption of the alveolar-capillary barrier, leading to poor gas exchange. Although the number of patients in need of lung transplantation is increasing, the number of donors is static. We investigated the potential to use gene therapy with an adenoviral vector encoding human interleukin-10 (AdhIL-10) to repair injured donor lungs ex vivo before transplantation. IL-10 is an anti-inflammatory cytokine that mainly exerts its suppressive functions by the inactivation of antigen-presenting cells with consequent inhibition of proinflammatory cytokine secretion. In pigs, AdhIL-10-treated lungs exhibited attenuated inflammation and improved function after transplantation. Lungs from 10 human multiorgan donors that had suffered brain death were determined to be clinically unsuitable for transplantation. They were then maintained for 12 hours at body temperature in an ex vivo lung perfusion system with or without intra-airway delivery of AdhIL-10 gene therapy. AdhIL-10-treated lungs showed significant improvement in function (arterial oxygen pressure and pulmonary vascular resistance) when compared to controls, a favorable shift from proinflammatory to anti-inflammatory cytokine expression, and recovery of alveolar-blood barrier integrity. Thus, treatment of injured human donor lungs with the cytokine IL-10 can improve lung function, potentially rendering injured lungs suitable for transplantation into patients. PMID: 20368171 [PubMed - indexed for MEDLINE] | | |
| Regulating in vivo calcification of alginate microbeads.
July 14, 2010 at 7:35 AM
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| | Regulating in vivo calcification of alginate microbeads. Biomaterials. 2010 Jun;31(18):4926-34 Authors: Lee CS, Moyer HR, Gittens RA, Williams JK, Boskey AL, Boyan BD, Schwartz Z Alginate calcification has been previously reported clinically and during animal implantation; however no study has investigated the mechanism, extensively characterized the mineral, or evaluated multiple methods to regulate or eliminate mineralization. In the present study, alginate calcification was first studied in vitro: calcium-crosslinked alginate beads sequestered surrounding phosphate while forming traces of hydroxyapatite. Calcification in vivo was then examined in nude mice using alginate microbeads with and without adipose stem cells (ASCs). Variables included the delivery method, site of delivery, sex of the animal, time in vivo, crosslinking solution, and method of storage prior to delivery. Calcium-crosslinked alginate microbeads mineralized when injected subcutaneously or implanted intramuscularly after 1-6 months. More extensive analysis with histology, microCT, FTIR, XRD, and EDS showed calcium phosphate deposits throughout the microbeads with surface mineralization that closely matched hydroxyapatite found in bone. Incorporating 25 mm bisphosphonate reduced alginate calcification whereas using barium chloride eliminated mineralization. Buffering the crosslinking solution with HEPES at pH 7.3 while washing and storing samples in basal media prior to implantation also eliminated calcification in vivo. This study shows that alginate processing prior to implantation can significantly influence bulk hydroxyapatite formation and presents a method to regulate alginate calcification. PMID: 20363022 [PubMed - indexed for MEDLINE] | | |
| A tissue-engineered trachea derived from a framed collagen scaffold, gingival fibroblasts and adipose-derived stem cells.
July 14, 2010 at 7:35 AM
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| | A tissue-engineered trachea derived from a framed collagen scaffold, gingival fibroblasts and adipose-derived stem cells. Biomaterials. 2010 Jun;31(18):4855-63 Authors: Kobayashi K, Suzuki T, Nomoto Y, Tada Y, Miyake M, Hazama A, Wada I, Nakamura T, Omori K In some types of tracheal disease, tracheal resection is required. For patients with tracheal resection, artificial grafts, made from collagen sponge with a spiral polypropylene stent and mesh, have been clinically used by our group. However, epithelial regeneration was confirmed to be slow. In the present study, we investigated the potential of gingival fibroblasts (GFBs) and adipose-derived stem cells (ASCs) as autologous transplanted cells in combination with artificial graft for tracheal epithelial regeneration. In in vitro co-culturing with tracheal epithelial cells, GFBs stimulated epithelial cell differentiation and reconstruction of a pseudostratified epithelium. ASCs stimulated epithelial cell proliferation and reconstruction of a multi-layered epithelium. Subsequently, we prepared three kinds of bioengineered scaffolds from GFBs and/or ASCs and implanted them into rat tracheal defects. The bioengineered scaffolds containing GFBs were covered with tracheal epithelial cells after 1 week, and highly ciliated epithelium was formed after 2 weeks of transplantation. The bioengineered scaffold containing ASCs induced thick epithelium, and then pseudostratified epithelium containing goblet cells was formed. Furthermore, the application of both GFBs and ASCs had synergistic effects on tracheal epithelial regeneration, suggesting that bioengineered scaffolds containing GFBs and ASCs are useful for hastening tracheal epithelial regeneration. PMID: 20347137 [PubMed - indexed for MEDLINE] | | |
| Decoupled control of stiffness and permeability with a cell-encapsulating poly(ethylene glycol) dimethacrylate hydrogel.
July 14, 2010 at 7:35 AM
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| | Decoupled control of stiffness and permeability with a cell-encapsulating poly(ethylene glycol) dimethacrylate hydrogel. Biomaterials. 2010 Jun;31(18):4864-71 Authors: Cha C, Kim SY, Cao L, Kong H Hydrogels are increasingly used as a cell encapsulation and transplantation device. The successful use of a hydrogel greatly relies on an ability to control hydrogel stiffness which affects structural integrity and regulates cellular phenotypes. However, conventional strategies to increase the gel stiffness lead to decrease in the gel permeability and subsequently deteriorate the viability of cells encapsulated in a gel matrix. This study presents a strategy to decouple the inversed dependency of permeability on the stiffness of a hydrogel by chemically cross-linking methacrylic alginate with poly(ethylene glycol) dimethacrylate (PEGDA). As expected, gel stiffness represented by elastic modulus was tuned over one order of magnitude with the concentration of methacrylic alginate and the degree of substitution of methacrylic groups. In contrast, swelling ratio of the hydrogel indicative of gel permeability was minimally changed because of multiple hydrophilic groups of alginate, similar to function of proteoglycans in a natural extracellular matrix. Furthermore, viability of neural cells encapsulated in a hydrogel of PEGDA and methacrylic alginate rather increased with hydrogel stiffness. Overall, the results of this study demonstrate an advanced biomaterial design paradigm which allows one to culture cells in a 3D matrix of varying rigidity. This study will therefore greatly expedite the use of a hydrogel system in both fundamental studies and clinical settings of cell therapies. PMID: 20347136 [PubMed - indexed for MEDLINE] | | |
| Primate mandibular reconstruction with prefabricated, vascularized tissue-engineered bone flaps and recombinant human bone morphogenetic protein-2 implanted in situ.
July 14, 2010 at 7:35 AM
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| | Primate mandibular reconstruction with prefabricated, vascularized tissue-engineered bone flaps and recombinant human bone morphogenetic protein-2 implanted in situ. Biomaterials. 2010 Jun;31(18):4935-43 Authors: Zhou M, Peng X, Mao C, Xu F, Hu M, Yu GY Several studies have validated successful mandibular reconstruction with prefabricated tissue-engineered bone flaps and recombinant human bone morphogenetic protein-2 (rhBMP-2) implanted in situ. Whether rhBMP-2 applied with the prefabrication technique enables faster ossification of mandibular defects than rhBMP-2 applied in situ is unknown. We aimed to compare mandibular reconstruction with prefabricated, vascularized tissue-engineered bone flaps with rhBMP-2 and rhBMP-2 applied in situ in primates (Rhesus monkey). We also compared the use of the carriers demineralized freeze-dried bone allograft (DFDBA) and coralline hydroxyapatite (CHA) for applying rhBMP-2. After computed tomography of the monkey head, custom meshes were made, loaded with rhBMP-2-incorporated DFDBA or CHA, and implanted in the latissimus dorsi muscle. Meanwhile, contralateral segmental mandibular defects were created, and custom meshes loaded with DFDBA, CHA, or rhBMP-2-incooperated DFDBA and CHA were implanted in situ. Thirteen weeks later, the bone flaps with rhBMP-2-incorporated DFDBA or CHA were transferred to repair segmental mandibular defects. The meshes loaded with DFDBA or CHA alone showed no bone regeneration 13 weeks after implantation in latissimus dorsi muscle. Radiography, angiography and histological analysis were used to evaluate the repair and vascularization of the implant. Segmental mandibular defects were successfully restored with prefabricated bone flaps and rhBMP-2-incorporated CHA in situ, but other segmental mandibular defects remained with rhBMP-2-incorporated DFDBA, DFDBA and CHA in situ. Moreover, mandibles reconstructed with rhBMP-2-incorporated CHA bone flaps revealed more regenerated and homogeneous bone formation than did other reconstructions. The study suggested that the prefabrication technique induced better mandibular reconstruction and bone regeneration in quantity and quality. PMID: 20346504 [PubMed - indexed for MEDLINE] | | |
| Mesenchymal stem cell seeded knitted silk sling for the treatment of stress urinary incontinence.
July 14, 2010 at 7:35 AM
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| | Mesenchymal stem cell seeded knitted silk sling for the treatment of stress urinary incontinence. Biomaterials. 2010 Jun;31(18):4872-9 Authors: Zou XH, Zhi YL, Chen X, Jin HM, Wang LL, Jiang YZ, Yin Z, Ouyang HW Stress urinary incontinence remains a worldwide problem affecting patients of all ages. Implantation of suburethral sling is the cornerstone treatment. Current slings have inherent disadvantages. This study aims to develop a tissue engineered sling with bone marrow derived mesenchymal stem cell seeded degradable silk scaffold. The mesenchymal stem cells were obtained from Sprague-Dawley rats and were characterized in vitro. Layered cell sheets were formed after two weeks of culture and were labeled with carboxyfluorescein diacetate. Forty female rats were divided into four groups: Group A (n=5) had sham operation; other three groups underwent bilateral proximal sciatic nerve transection and were confirmed with stress urinary incontinence by the leak-point pressure measurement at 4 weeks after operation. Then, Group B (n=5) had no sling placed; Group C (n=15) was treated with a silk sling; and Group D (n=15) was treated with the tissue engineered sling. Histology and the leak-point pressure measurements were done at 4 and 12 weeks after the sling implantation while collagen content and mechanical testing were done at 12 weeks. The results showed that Group B had a significantly lower leak-point pressure (24.0+/-4.2 cmH(2)O) at 4 weeks (P<0.05), while Group C (38.0+/-3.3 cmH(2)O) and Group D (36.3+/-3.1 cmH(2)O) almost reached to the normal level shown by Group A (41.6+/-3.8 cmH(2)O) (p>0.05). At 12 weeks, tissue engineered sling of group D has higher collagen content (70.84+/-14.49 microg/mg) and failure force (2.436+/-0.192 N) when compared those of Group C (38.94+/-7.05 microg/mg and 1.521+/-0.087 N) (p<0.05). Both the silk sling and tissue engineered sling showed convincing functional effects for the treatment of stress urinary incontinence in a rat model. And the better ligament-like tissue formation in the tissue engineered sling suggested potential long-term function. PMID: 20303586 [PubMed - indexed for MEDLINE] | | |
| [Preliminary study on tissue-engineered cartilage with human dermal fibroblasts co-cultured with porcine chondrocytes in vitro]
July 14, 2010 at 7:35 AM
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| | [Preliminary study on tissue-engineered cartilage with human dermal fibroblasts co-cultured with porcine chondrocytes in vitro] Zhonghua Zheng Xing Wai Ke Za Zhi. 2009 Nov;25(6):447-51 Authors: Liu X, Zhou GD, Liu W, Cao YL OBJECTIVE: To explore the feasibility of constructing tissue-engineered cartilage with human dermal fibroblasts (HDFs) in vitro. METHODS: Porcine articular chondrocytes and HDFs were isolated and in vitro expanded respectively. Then they were mixed at the ratio of 1:1 (chondrocytes: fibroblasts) . The mixed cells were seeded onto polyglycolic acid (PGA) scaffold at the ultimate concentration of 5.0 x 10(7)/ml as co-culture group. Chondrocytes and HDFs at the same ultimate concentration were seeded respectively onto the scaffold as chondrocyte group ( positive control group) and fibroblast group ( negative control group). The specimens were collected after in vitro culture for 8 weeks. Gross observation, histology and immunohistochemistry were used to evaluate the results. RESULTS: In chondrocyte group, the cell-scaffold constructs could maintain the original size and shape during in vitro culture. The new formed cartilage-like tissue had typical histological structure and extracellular matrix staining similar to normal cartilage. In co-culture group the constructs shrunk slightly at 8 weeks, cartilage-like tissue formed and GAG could be detected for strong expression by Safranin O staining. Furthermore, using the specific identification, a few HDFs derived cells were found to form lacuna structure at the peripheral area of cartilage-like tissue. In fibroblast group, the constructs deformed and shrunk gradually without mature cartilage lacuna in histology. CONCLUSION: The 3D-co-culture system can effectively induce the differentiation of HDFs to chondrocytes. The tissue-engineered cartilage can be constructed in vitro with the 3D-co-culture system. PMID: 20209938 [PubMed - indexed for MEDLINE] | | |
| Challenges in regenerative endodontics: a case series.
July 14, 2010 at 7:35 AM
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| | Challenges in regenerative endodontics: a case series. J Endod. 2010 Mar;36(3):536-41 Authors: Petrino JA, Boda KK, Shambarger S, Bowles WR, McClanahan SB INTRODUCTION: An immature tooth with pulpal necrosis and apical periodontitis presents a unique challenge to the endodontist. Endodontic treatment options consist of apexification, apical barriers, or more recently, revascularization. The purpose of this case series is to report three cases that used revascularization protocol as described by Banchs and Trope. Each case presented its own special circumstances and challenges. The lessons learned from each case provided guidance for more predictable outcomes on subsequent cases. METHODS: Six immature teeth with apical periodontitis (in three patients) were treated via the revascularization protocol using irrigants, a triple antibiotic paste, and a coronal seal of mineral trioxide aggregate and composite. RESULTS: For follow-up, all six teeth showed resolution of periapical radiolucencies, whereas three of six teeth showed continued root development. Two teeth displayed a positive response to vitality testing. CONCLUSIONS: Results from this case series show that revascularization is a technically challenging but effective treatment modality for the immature tooth with apical periodontitis. Based on this case series, the following recommendations are made to help with the revascularization technique: (1) clinicians should consider the use of an anesthetic without a vasoconstrictor when trying to induce bleeding, (2) a collagen matrix is useful for the controlled placement of MTA to a desired and optimal level, (3) patients/parents should be informed about the potential for staining, especially in anterior teeth when the paste contains minocycline, and (4) patient/parent compliance with the necessary multiple appointment treatment plan may be significant for case selection. PMID: 20171379 [PubMed - indexed for MEDLINE] | | |
| Regulatory T cells contribute to the protective effect of ischemic preconditioning in the kidney.
July 14, 2010 at 7:35 AM
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| | Regulatory T cells contribute to the protective effect of ischemic preconditioning in the kidney. Kidney Int. 2010 May;77(9):771-80 Authors: Kinsey GR, Huang L, Vergis AL, Li L, Okusa MD Reperfusion following ischemia is associated with acute kidney injury and inflammation. Using a mouse model, we exposed the kidney to a nonlethal period of ischemia, rendering it refractory to future ischemia-induced dysfunction. This ischemic preconditioning is partially mediated by Treg lymphocytes that suppress immune responses. We found that this maneuver significantly inhibited the accumulation of neutrophils and macrophages, tubular necrosis, and loss of kidney function caused by a subsequent ischemia/reperfusion injury 1 week later. The initial ischemia/reperfusion caused a significant increase in CD4(+)CD25(+)FoxP3(+) and CD4(+)CD25(+)IL-10(+) Treg cells within the kidney at 7 days of reperfusion. Treatment of preconditioned mice with a Treg cell-depleting antibody (PC61) reversed the effect of preconditioning on kidney neutrophil accumulation and partially inhibited the functional and histological protection of preconditioning. Adoptive transfer of Treg cells in naive mice, before ischemia/reperfusion, mimicked the protective and anti-inflammatory effects of ischemic preconditioning on the kidney. These studies highlight the role of Treg cells in ischemic preconditioning. PMID: 20164824 [PubMed - indexed for MEDLINE] | | |
| Thermally-triggered gelation of PLGA dispersions: towards an injectable colloidal cell delivery system.
July 14, 2010 at 7:35 AM
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| | Thermally-triggered gelation of PLGA dispersions: towards an injectable colloidal cell delivery system. J Colloid Interface Sci. 2010 Apr 1;344(1):61-9 Authors: Fraylich MR, Liu R, Richardson SM, Baird P, Hoyland J, Freemont AJ, Alexander C, Shakesheff K, Cellesi F, Saunders BR In this study the properties of poly(D,L-lactide-co-glycolide) (PLGA) dispersions containing a thermoresponsive cationic copolymer were investigated. The PLGA dispersions were prepared by interfacial deposition in aqueous solution and were rendered thermoresponsive by addition of a cationic poly(N-isopropyl acrylamide) (PNIPAm) graft copolymer. The copolymers used had the general composition PDMA(x)(+)-g-(PNIPAm(n))(y). DMA(+) is quarternarized N,N-dimethylaminoethyl methacrylate. The PDMA(x)(+)-g-(PNIPAm(n))(y) copolymers have x and y values that originate from the macroinitiator used for their preparation; values for n correspond to the PNIPAm arm length. The thermoresponsive dispersions were characterised using photon correlation spectroscopy, turbidity measurements and electrophoretic mobility measurements. A strong electrostatic attraction between the anionic PLGA particles and cationic copolymer was present and the dispersions showed thermally-triggered gelation at total polymer volume fractions as low as 0.015. These new PLGA gels, which formed at about 32 degrees C, had elastic modulus values that could be controlled using dispersion composition. Scanning electron micrographs of the gels showed high porosity and interconnectivity of elongated pores. Remarkably, the gels were flexible and had critical yield strains as high as 160%. The ability of the gels to support growth of bovine nucleus pulposus cells was investigated using two-dimensional cell culture. The cells proliferated and remained viable on the gels after 3days. The results suggest that this general family of biodegradable thermogelling PLGA dispersions, introduced here for the first time, may have longer-term application as an injectable colloidal cell delivery system. PMID: 20070971 [PubMed - indexed for MEDLINE] | | |
| Young adult chondrocytes proliferate rapidly and produce a cartilaginous tissue at the gel-media interface in agarose cultures.
July 14, 2010 at 7:35 AM
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| | Young adult chondrocytes proliferate rapidly and produce a cartilaginous tissue at the gel-media interface in agarose cultures. Connect Tissue Res. 2010 Jun;51(3):216-23 Authors: Tran-Khanh N, Chevrier A, Lascau-Coman V, Hoemann CD, Buschmann MD Primary chondrocytes cultured in agarose can escape the gel, accumulate at the interface between agarose and the culture medium, and form an outgrowing tissue. These outgrowths can appear as voluminous cartilage-like nodules that have never been previously investigated. In the present study, bovine articular chondrocytes from three age groups (fetal, young adult, aged) were seeded and cultured in agarose to test the hypothesis that hyaline-like cartilage outgrowths develop at the interface by appositional growth, in an age-dependant manner. Macroscopic appearance, cell content, cell division, cytoskeletal morphology, and extracellular matrix (ECM) composition were analyzed. Fetal chondrocytes produced a fibrous interfacial tissue while aged chondrocytes produced ECM-poor cell clusters. In contrast young adult chondrocytes produced large cartilaginous outgrowths, rich in proteoglycan and collagen II, where cells in the central region displayed a chondrocyte morphology. Cell proliferation was confined to the peripheral edge of these outgrowths, where elongated cell morphology, cell-cell contacts, and cell extensions toward the culture medium were seen. Thus these voluminous cartilaginous outgrowths formed in an appositional growth process and only for donor chondrocytes from young adult animals. This system offers an interesting ability to proliferate chondrocytes in a manner that results in a chondrocyte morphology and a cartilaginous ECM in central regions of the outgrowing tissue. It also provides an in vitro model system to study neocartilage appositional growth. PMID: 20053130 [PubMed - indexed for MEDLINE] | | |
| Activity-dependent neuroprotective protein (ADNP) expression in the amyloid precursor protein/presenilin 1 mouse model of Alzheimer's disease.
July 14, 2010 at 7:35 AM
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| | Activity-dependent neuroprotective protein (ADNP) expression in the amyloid precursor protein/presenilin 1 mouse model of Alzheimer's disease. J Mol Neurosci. 2010 May;41(1):114-20 Authors: Fernandez-Montesinos R, Torres M, Baglietto-Vargas D, Gutierrez A, Gozes I, Vitorica J, Pozo D A major determinant in the pathogenesis of Alzheimer's disease (AD) is the deposition of beta-amyloid (Abeta) peptides in specific areas of the central nervous system. Therefore, animal models of Alzheimer amyloidosis are excellent tools to identify candidates to facilitate drug screening and to understand the molecular pathology of AD. Activity-dependent neuroprotective protein (ADNP) plays an essential role in brain development, and NAP (NAPVSIPQ, generic name: davunetide)--a peptide derived from ADNP--is currently in clinical development for the treatment of neurodegenerative disorders. However, the link between ADNP expression and AD remains unexplored. To test whether ADNP is affected by the onset of AD and progression, we employed the PS1xAPP mouse model (PS1(M146L) x APP(751SL) transgenic mice) to analyze the mRNA expression of ADNP in the hippocampus and cerebellum in early and advanced stages of disease. Results showed that ADNP expression in 6-month-old PS1xAPP mice hippocampus was higher than in wild-type (WT) mice. ADNP was originally identified as a vasoactive intestinal peptide (VIP)-responsive gene taking part in the VIP-mediated neurotrophic pathway. Interestingly, the expression of VIP was not affected in the same experimental setting, suggesting that ADNP expression is a VIP-independent marker associated with AD. Moreover, in the cerebellum, a brain area not affected by Abeta deposition, ADNP mRNA expression in 6-month-old PS1xAPP and WT were not different. A similar extent of hippocampal ADNP expression was observed in 18-month-old WT and PS1xAPP mice, in contrast to the differential expression level at 6 months of age. However, hippocampal ADNP expression in both WT and PS1xAPP was increased with aging similar to VIP mRNA expression. Our findings support the hypothesis that ADNP expression is related to early or mild AD progression by a VIP-independent mechanism. PMID: 19844808 [PubMed - indexed for MEDLINE] | | |
| Adipose tissue-derived progenitors for engineering osteogenic and vasculogenic grafts.
July 14, 2010 at 7:35 AM
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| | Adipose tissue-derived progenitors for engineering osteogenic and vasculogenic grafts. J Cell Physiol. 2010 Jul 12; Authors: Scherberich A, Müller AM, Schäfer DJ, Banfi A, Martin I The current need for bone grafts in orthopedic and reconstructive surgery cannot be satisfied by autologous tissue transplant due to its limited availability and significant associated morbidity. Tissue engineering approaches could supply sufficient amounts of bone substitutes by exploiting the ability to harvest autologous osteogenic progenitors associated with suitable porous materials. However, the generation of clinically relevant-sized constructs is critically hampered by limited vascularization, with consequent engraftment and survival only of a thin outer shell, upon in vivo implantation. To overcome this limitation, different non-mutually exclusive approaches have recently been developed to promote or accelerate graft vascularization, from angiogenic growth factor gene delivery to surgical pre-vascularisation of the construct before implantation. A simple, promising strategy involves the co-culture of vasculogenic cells to form an intrinsic vascular network inside the graft in vitro, which can rapidly anastomose with the host blood vessels in vivo. Recent data have shown that adipose tissue-derived stromal vascular fraction (SVF) may provide an efficient, convenient and autologous source for both osteogenic and endothelial cells. When SVF progenitors were cultured in appropriate bioreactor systems and ectopically implanted, a functional vascular network connected to the host was formed concomitantly to bone formation. Future studies should aim at demonstrating that this approach effectively supports survival of scaled up cell-based bone grafts at an orthotopic site. The procedure should also be adapted to become compatible with an intra-operative timeline and complemented with the definition of suitable potency markers, to facilitate its development into a simplified, reproducible and cost-effective clinical treatment. J. Cell. Physiol. (c) 2010 Wiley-Liss, Inc. PMID: 20626000 [PubMed - as supplied by publisher] | | |
| Reactive oxygen species are involved in the IFN-gamma-stimulated production of Th2 chemokines in HaCaT keratinocytes.
July 14, 2010 at 7:35 AM
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| | Reactive oxygen species are involved in the IFN-gamma-stimulated production of Th2 chemokines in HaCaT keratinocytes. J Cell Physiol. 2010 Jul 12; Authors: Qi XF, Teng YC, Yoon YS, Kim DH, Cai DQ, Lee KJ The increased generation of reactive oxygen species (ROS) induces inflammation in different cell types. However, it is unclear whether ROS play an essential role in the production of thymus and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22) in keratinocytes. Here, we investigated the function of ROS in the production of these two Th2 chemokines in IFN-gamma-treated HaCaT keratinocytes. We found that IFN-gamma induced production of both chemokines in parallel with the increased generation of intracellular ROS. A ROS scavenger, N-acetyl-cysteine (NAC), significantly inhibited the IFN-gamma-induced production of chemokines as well as the activation of IkappaB-NF-kappaB. Inhibitors of Janus family kinases (JAKs), p38 mitogen-activated kinase (MAPK), and nuclear factor-kappa B (NF-kappaB) suppressed IFN-gamma-induced production of TARC and MDC. NF-kappaB activation was inhibited by both inhibitors of JAKs and p38 MAPK. Importantly, IFN-gamma-stimulated phosphorylation of p38 MAPK was significantly suppressed by JAKs inhibitors, but not significantly affected by NAC or L-buthionine sulfoximine (L-BSO). However, IFN-gamma-stimulated activation of I kappa-B (IkappaB) and NF-kappaB was suppressed by NAC but enhanced by BSO. Furthermore, inhibition of p38 MAPK and JAKs did not affect ROS generation in IFN-gamma-stimulated HaCaT cells. These results indicate that intracellular ROS and JAKs/p38 MAPK both contribute independently to IFN-gamma-stimulated production of TARC and MDC in HaCaT keratinocytes, by increasing NF-kappaB activation. (c) 2010 Wiley-Liss, Inc. PMID: 20625996 [PubMed - as supplied by publisher] | | |
| 2010 Nicolas Andry Award: Multipotent Adult Stem Cells from Adipose Tissue for Musculoskeletal Tissue Engineering.
July 14, 2010 at 7:35 AM
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| | 2010 Nicolas Andry Award: Multipotent Adult Stem Cells from Adipose Tissue for Musculoskeletal Tissue Engineering. Clin Orthop Relat Res. 2010 Jul 13; Authors: Guilak F, Estes BT, Diekman BO, Moutos FT, Gimble JM BACKGROUND: Cell-based therapies such as tissue engineering provide promising therapeutic possibilities to enhance the repair or regeneration of damaged or diseased tissues but are dependent on the availability and controlled manipulation of appropriate cell sources. QUESTIONS/PURPOSES: The goal of this study was to test the hypothesis that adult subcutaneous fat contains stem cells with multilineage potential and to determine the influence of specific soluble mediators and biomaterial scaffolds on their differentiation into musculoskeletal phenotypes. METHODS: We reviewed recent studies showing the stem-like characteristics and multipotency of adipose-derived stem cells (ASCs), and their potential application in cell-based therapies in orthopaedics. RESULTS: Under controlled conditions, ASCs show phenotypic characteristics of various cell types, including chondrocytes, osteoblasts, adipocytes, neuronal cells, or muscle cells. In particular, the chondrogenic differentiation of ASCs can be induced by low oxygen tension, growth factors such as bone morphogenetic protein-6 (BMP-6), or biomaterial scaffolds consisting of native tissue matrices derived from cartilage. Finally, focus is given to the development of a functional biomaterial scaffold that can provide ASC-based constructs with mechanical properties similar to native cartilage. CONCLUSIONS: Adipose tissue contains an abundant source of multipotent progenitor cells. These cells show cell surface marker profiles and differentiation characteristics that are similar to but distinct from other adult stem cells, such as bone marrow mesenchymal stem cells (MSCs). CLINICAL RELEVANCE: The availability of an easily accessible and reproducible cell source may greatly facilitate the development of new cell-based therapies for regenerative medicine applications in the musculoskeletal system. PMID: 20625952 [PubMed - as supplied by publisher] | | |
| Thermoresponsive poly(N-vinylcaprolactam) cryogels: synthesis and its biophysical evaluation for tissue engineering applications.
July 14, 2010 at 7:35 AM
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| | Thermoresponsive poly(N-vinylcaprolactam) cryogels: synthesis and its biophysical evaluation for tissue engineering applications. J Mater Sci Mater Med. 2010 Jul 13; Authors: Srivastava A, Kumar A The thermoresponsive poly(N-vinylcaprolactam) (PVCl) based cryogel network were synthesized and characterized with respect to physical and biological properties. The PVCl cryogel crosslinked with polyethylene glycol-diacrylate (PEGda) was synthesized in 1% dimethyl sulfoxide containing aqueous medium at -12 degrees C for 12-14 h. The cryogel synthesized in this manner were highly spongy in nature and can absorb water in its porous network. These polymeric cryogel networks have good physical morphology as confirmed by scanning electron microscopy. The estimated porosity of these cryogels was 90% as demonstrated by various methods based on absorption of water and cyclohexane. The median pore diameter and surface area was 30 mum and 2.0253 m(2)/g, respectively as confirmed by analysis on mercury porosimeter. These materials can interact with biological system without any cytotoxic effects. Change in temperature influenced the adsorption of fetal bovine serum (FBS) on PVCl scaffold which showed maximum protein adsorption at 37 degrees C, as compared to that at 25 degrees C. Furthermore, the fibroblast cell adhesion studies showed the potential of these PVCl based cryogels as tissue engineering scaffolds. PMID: 20625836 [PubMed - as supplied by publisher] | | |
| Association of polymorphisms of zinc metalloproteinases with clinical response to stem cell therapy.
July 14, 2010 at 7:35 AM
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| | Association of polymorphisms of zinc metalloproteinases with clinical response to stem cell therapy. Herz. 2010 Jul 14; Authors: Panovsky R, Vasku A, Meluzin J, Kaminek M, Mayer J, Janousek S, Kincl V, Groch L, Navratil M AIM: The purpose of this study was to assess the associations of polymorphisms in two metalloproteinase genes-metalloproteinase-2 (MMP-2) and angiotensin converting enzyme (ACE)-with clinical response to autologous transplantation of mononuclear bone marrow cells (MBMC) in patients with acute myocardial infarction. METHODS: The double centre study included 48 patients with a first acute myocardial infarction treated with primary coronary angioplasty, stent implantation and transplantation of MBMC. According to the changes in perfusion defect size, left ventricle ejection fraction, end-systolic volume and peak systolic velocity of the infracted wall (dSaMI) after cell therapy, the patients were retrospectively divided into group A (responders) and group B (non-responders). Genomic DNA was isolated from peripheral leukocytes by a standard technique using proteinase K. Three MMP-2 promoter (-1575G/A, -1306C/T and -790T/G) as well as I/D ACE gene polymorphisms were detected by PCR methods with restriction analyses (when necessary) according to standard protocols. RESULTS: Of the 48 patients who received MBMC transplantation, 17 responded to the therapy. There were no significant differences in the prevalence of matrix metalloproteinase-2 triple genotype GGCCTT between responder/non-responder groups (71% versus 61%, p=0.375). Similarly, no differences in either genotype distribution or allelic frequencies of I/D ACE polymorphism between responders and non-responders to the cell therapy were observed (p=0.933). Compared to patients with ACE genotype ID or DD, the patients with ACE II genotype significantly improved in regional systolic LV function of the infarcted wall after implantations of MBMC (dSaMI - 0.4 versus 1.4 cm/s, p=0.037). CONCLUSION: In our study, the ACE genotype II was associated with improvement of regional systolic LV function of the infarcted wall after implantations of MBMC. The detected polymorphism in matrix metalloproteinase-2 gene was not associated with clinical response to cell therapy. PMID: 20625691 [PubMed - as supplied by publisher] | | |
| [Surgical intramyocardial stem cell therapy for chronic ischemic heart failure.]
July 14, 2010 at 7:35 AM
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| | [Surgical intramyocardial stem cell therapy for chronic ischemic heart failure.] Herz. 2010 Jul 14; Authors: Kaminski A, Donndorf P, Klopsch C, Steinhoff G Chronic ischemic heart disease patients are already being treated worldwide with bone marrow stem cells both in the context of clinical studies and in therapy trials. By combining this therapy with established revascularization procedures such as bypass surgery, a high level of patient safety can be achieved. To date, no stem cell-related cardiac complications following intramyocardial injection of bone marrow-derived stem cells during CABG (coronary artery bypass graft) surgery have been reported. The functional advantage conferred by surgical bone marrow stem cell therapy is a 7.2% increase in LVEF (left ventricular ejection fraction) compared to controls. Randomized placebo-controlled trials, like the German trial PERFECT, are needed to obtain a more evidence-based assessment of this therapy. PMID: 20625690 [PubMed - as supplied by publisher] | | |
| Nonviral gene delivery to mesenchymal stem cells using cationic liposomes for gene and cell therapy.
July 14, 2010 at 7:35 AM
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| | Nonviral gene delivery to mesenchymal stem cells using cationic liposomes for gene and cell therapy. J Biomed Biotechnol. 2010;2010:735349 Authors: Madeira C, Mendes RD, Ribeiro SC, Boura JS, Aires-Barros MR, da Silva CL, Cabral JM Mesenchymal stem cells (MSCs) hold a great promise for application in several therapies due to their unique biological characteristics. In order to harness their full potential in cell-or gene-based therapies it might be advantageous to enhance some of their features through gene delivery strategies. Accordingly, we are interested in developing an efficient and safe methodology to genetically engineer human bone marrow MSC (BM MSC), enhancing their therapeutic efficacy in Regenerative Medicine. The plasmid DNA delivery was optimized using a cationic liposome-based reagent. Transfection efficiencies ranged from ~2% to ~35%, resulting from using a Lipid/DNA ratio of 1.25 with a transgene expression of 7 days. Importantly, the number of plasmid copies in different cell passages was quantified for the first time and ~20,000 plasmid copies/cell were obtained independently of cell passage. As transfected MSC have shown high viabilities (>90%) and recoveries (>52%) while maintaining their multipotency, this might be an advantageous transfection strategy when the goal is to express a therapeutic gene in a safe and transient way. PMID: 20625411 [PubMed - in process] | | |
| Arsenic antagonizes the Hedgehog pathway by preventing ciliary accumulation and reducing stability of the Gli2 transcriptional effector.
July 14, 2010 at 7:35 AM
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| | Arsenic antagonizes the Hedgehog pathway by preventing ciliary accumulation and reducing stability of the Gli2 transcriptional effector. Proc Natl Acad Sci U S A. 2010 Jul 12; Authors: Kim J, Lee JJ, Kim J, Gardner D, Beachy PA Aberrant Hedgehog (Hh) pathway activation has been implicated in cancers of diverse tissues and organs, and the tumor growth-inhibiting effects of pathway antagonists in animal models have stimulated efforts to develop pathway antagonists for human therapeutic purposes. These efforts have focused largely on cyclopamine derivatives or other compounds that mimic cyclopamine action in binding to and antagonizing Smoothened, a membrane transductory component. We report here that arsenicals, in contrast, antagonize the Hh pathway by targeting Gli transcriptional effectors; in the short term, arsenic blocks Hh-induced ciliary accumulation of Gli2, the primary activator of Hh-dependent transcription, and with prolonged incubation arsenic reduces steady-state levels of Gli2. Arsenicals active in Hh pathway antagonism include arsenic trioxide (ATO), a curative agent in clinical use for acute promyelocytic leukemia (APL); in our studies, ATO inhibited growth of Hh pathway-driven medulloblastoma allografts derived from Ptch(+/-)p53(-/-) mice within a range of serum levels comparable to those achieved in treatment of human APL. Arsenic thus could be tested rapidly as a therapeutic agent in malignant diseases associated with Hh pathway activation and could be particularly useful in such diseases that are inherently resistant or have acquired resistance to cyclopamine mimics. PMID: 20624968 [PubMed - as supplied by publisher] | | |
| Cell Compatibility of Fibrin Sealants:In Vitro Study with Cells Involved in Soft Tissue Repair.
July 14, 2010 at 7:35 AM
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| | Cell Compatibility of Fibrin Sealants:In Vitro Study with Cells Involved in Soft Tissue Repair. J Biomater Appl. 2010 Jul 12; Authors: Macasev D, Diorio JP, Gugerell A, Goppelt A, Gulle H, Bittner M Fibrin sealants can be used to support tissue regeneration or as vehicles for delivery of cells in tissue engineering. Differences in the composition of fibrin sealants, however, could determine the success of such applications. The results presented in this article show clear differences between Fibrin sealant A (FS A) clots and Fibrin sealant B (FS B) clots with respect to their compatibility with primary human cells involved in soft tissue repair. FS A clots, which are characterized by a physiological coarse fibrin structure, promoted attachment, spreading, and proliferation of keratinocytes, fibroblasts, and endothelial cells. In contrast, FS B clots displaying a fine to medium clot structure failed to support spreading of all three cell types. Adhesion of keratinocytes was decreased on FS B clots compared to FS A clots after 3 h incubation, whereas number of attached fibroblasts and endothelial cells was initially comparable between the two fibrin sealants. However, all three cell types proliferated on FS A clots but no sustained proliferation was detected on FS B clots. We further demonstrate that the observed differences between FS A and B clots are partly based upon 1 M sodium chloride extractable constituents, like thrombin, and partly on nonextractable constituents or the fibrin structure. In conclusion, our in vitro results demonstrate that FS A clots serve as a provisional matrix that encourages adhesion and growth of keratinocytes, fibroblasts, and endothelial cells. Therefore, FS A seems to be well suited for applications in tissue engineering. PMID: 20624847 [PubMed - as supplied by publisher] | | |
| Osteoclast and Osteoblast Activities on Carbonate Apatite Plates in Cell Cultures.
July 14, 2010 at 7:35 AM
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| | Osteoclast and Osteoblast Activities on Carbonate Apatite Plates in Cell Cultures. J Biomater Appl. 2010 Jul 12; Authors: Kanayama K, Sriarj W, Shimokawa H, Ohya K, Doi Y, Shibutani T Previous studies have demonstrated that carbonate apatite (CA) is superior to hydroxyapatite (HA) and beta-tricalciumphosphate (beta-TCP) with regard to osteoclastic resorption, but evidence on osteoclast and osteoblast response remains controversial. In the present study, the expression of bone related mRNA is examined on CA, HA, beta-TCP, and titanium plates. ICR mouse osteoblast cells are cocultured with ICR mouse bone marrow cells. Crude osteoclast-like cell-rich suspensions are then seeded onto plates and cultured for 48 h. Total RNA is extracted and mRNA expression is examined by real-time RT-PCR. Amounts of vacuolar-type ATPase, cathepsin K, and TRAP mRNA are significantly greater on CA than on the other plates. The amount of osteoprotegerin mRNA is significantly greater on CA than on the other plates. RANKL mRNA expression, which is generally regarded as an osteoblast maker, varies with material, but shows no significant differences between CA and the other plates. The formation and activity of osteoclasts is greater with CA than with the other plates. Thus, CA is superior to beta-TCP as a bioresorbable bone substitute for tissue engineering. PMID: 20624844 [PubMed - as supplied by publisher] | | |
| CD34+ cell mobilization and upregulation of myocardial cytokines in a rabbit model of myocardial ischemia.
July 14, 2010 at 7:35 AM
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| | CD34+ cell mobilization and upregulation of myocardial cytokines in a rabbit model of myocardial ischemia. Int J Cardiol. 2010 Jul 10; Authors: Zhao Q, Sun C, Xu X, Zhou J, Wu Y, Tian Y, Yuan Z, Liu Z BACKGROUND: Studies have suggested that myocardial infarction may induce bone marrow stem cell mobilization and homing to the infarcted area, contributing to myocardial repair and tissue regeneration. Despite some encouraging results using stem cell therapy for myocardial regeneration in humans and animals, the mechanisms behind this activity remain unclear. In this study, we investigate stem cell mobilization and homing in ischemic myocardium, and investigate the involvement of cytokines TNFalpha and VEGF in this process. METHODS AND RESULTS: Myocardial ischemia models were created by partial ligation of the left anterior descending coronary artery in Japanese white male rabbits. Immunohistochemistry analysis of ischemic myocardium showed the presence of VEGF and TNFalpha along with homing of CD34 positive (CD34+) cells to the region in the 7days following surgery. During the same period, an increase in percentage of CD34+ cells in peripheral blood and in VEGF and TNFalpha mRNA expression in ischemic tissue was observed in animals that underwent partial LAD ligation. Terminal dUTP nick end-labeling (TUNEL) showed that cell apoptosis in the ischemic myocardium decreased between days 7 and 28 following surgery. None of these changes were observed in animals that underwent sham operation. CONCLUSIONS: In the early stages of myocardial ischemia, bone marrow stem cells are mobilized and home to ischemic myocardium with a concomitant increase in expression of cytokines VEGF and TNFalpha. Furthermore, cell apoptosis occurs in the ischemic myocardium, possibly due to the activity of TNFalpha which is thought to induce cardiomyocyte apoptosis. PMID: 20624659 [PubMed - as supplied by publisher] | | |
| Tbx3: another important piece fitted into the pluripotent stem cell puzzle.
July 14, 2010 at 7:35 AM
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| | Tbx3: another important piece fitted into the pluripotent stem cell puzzle. Stem Cell Res Ther. 2010 May 20;1(2):12 Authors: Pirity MK, Dinnyes A ABSTRACT: Induced pluripotent stem cells (iPSCs) are novel tools for biomedical research, with a promise for future regenerative medicine applications. Recently, Han and colleagues reported in Nature that T box gene 3 (Tbx3) can improve the quality of mouse iPSCs and increase their germline transmission efficacy. This observation contributes greatly to the improvement of iPSC technology and might be a step towards 'designer' reprogramming strategies by generating high quality iPSCs. Further studies comparing pluripotency regulation in different species, including that in human, will be necessary to verify the universal role of Tbx3 and the medical relevance of the observation. PMID: 20624271 [PubMed - as supplied by publisher] | | |
| Stem cell therapies to treat muscular dystrophy: progress to date.
July 14, 2010 at 7:35 AM
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| | Stem cell therapies to treat muscular dystrophy: progress to date. BioDrugs. 2010 Aug 1;24(4):237-47 Authors: Meregalli M, Farini A, Parolini D, Maciotta S, Torrente Y Muscular dystrophies are heritable, heterogeneous neuromuscular disorders and include Duchenne and Becker muscular dystrophies (DMD and BMD, respectively). DMD patients exhibit progressive muscle weakness and atrophy followed by exhaustion of muscular regenerative capacity, fibrosis, and eventually disruption of the muscle tissue architecture. In-frame mutations in the dystrophin gene lead to expression of a partially functional protein, resulting in the milder BMD. No effective therapies are available at present. Cell-based therapies have been attempted in an effort to promote muscle regeneration, with the hope that the host cells would repopulate the muscle and improve muscle function and pathology. Injection of adult myoblasts has led to the development of new muscle fibers, but several limitations have been identified, such as poor cell survival and limited migratory ability. As an alternative to myoblasts, stem cells were considered preferable for therapeutic applications because of their capacity for self-renewal and differentiation potential. In recent years, encouraging results have been obtained with adult stem cells to treat human diseases such as leukemia, Parkinson's disease, stroke, and muscular dystrophies. Embryonic stem cells (ESCs) can be derived from mammalian embryos in the blastocyst stage, and because they can differentiate into a wide range of specialized cells, they hold potential for use in treating almost all human diseases. Several ongoing studies focus on this possibility, evaluating differentiation of specific cell lines from human ESCs (hESCs) as well as the potential tumorigenicity of hESCs. The most important limitation with using hESCs is that it requires destruction of human blastocysts or embryos. Conversely, adult stem cells have been identified in various tissues, where they serve to maintain, generate, and replace terminally differentiated cells within their specific tissue as the need arises for cell turnover or from tissue injury. Moreover, these cells can participate in regeneration of more than just their specific tissue type. Here we describe multiple types of muscle- and fetal-derived myogenic stem cells, their characterization, and their possible use in treating muscular dystrophies such as DMD and BMD. We also emphasize that the most promising possibility for the management and therapy of DMD and BMD is a combination of different approaches, such as gene and stem cell therapy. PMID: 20623990 [PubMed - in process] | | |
| Platelet-rich fibrin modulates the expression of extracellular signal-regulated protein kinase and osteoprotegerin in human osteoblasts.
July 14, 2010 at 7:35 AM
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| | Platelet-rich fibrin modulates the expression of extracellular signal-regulated protein kinase and osteoprotegerin in human osteoblasts. J Biomed Mater Res A. 2010 Jul 8; Authors: Chang IC, Tsai CH, Chang YC Platelet-rich fibrin (PRF) by Choukroun's technique is produced in a totally natural manner, without using anticoagulant during blood harvest nor bovine thrombin and calcium chloride for platelet activation and fibrin polymerization. When delicately pressed between two gauzes, the PRF clot becomes a strong membrane with high potential in clinical application and tissue engineering. In this study, blood collection was carried out from healthy volunteers. Osteoblast cell line U2OS was used to evaluate the cell proliferation resulting from PRF by using colorimetric assay. Western blot was employed to evaluate the expression of phosphorylated extracellular signal-regulated protein kinase (p-ERK), receptor activator of nuclear factor-kappa B ligand (RANKL), and osteoprotegerin (OPG) in U2OS cells. PRF was found to increase osteoblast proliferation during 5 day incubation period (p < 0.05). PRF was found to increase ERK phosphorylation in U2OS cells (p < 0.05). OPG was significantly elevated by the stimulation with PRF (p < 0.05). However, there was no significant change in RANKL expression (p > 0.05). Taken together, PRF can stimulate osteoblasts proliferation. The activation of p-ERK and OPG expression by PRF suggests a potential role for new bone formation. The application of PRF may provide the benefit for the bone regeneration. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 20623670 [PubMed - as supplied by publisher] | | |
| Germline self-renewal requires cyst stem cells and stat regulates niche adhesion in Drosophila testes.
July 14, 2010 at 7:35 AM
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| | Germline self-renewal requires cyst stem cells and stat regulates niche adhesion in Drosophila testes. Nat Cell Biol. 2010 Jul 11; Authors: Leatherman JL, Dinardo S Adults maintain tissue-specific stem cells through niche signals. A model for niche function is the Drosophila melanogaster testis, where a small cluster of cells called the hub produce locally available signals that allow only adjacent cells to self-renew. We show here that the principal signalling pathway implicated in this niche, chemokine activation of STAT, does not primarily regulate self-renewal of germline stem cells (GSCs), but rather governs GSC adhesion to hub cells. In fact, GSC renewal does not require hub cell contact, as GSCs can be renewed solely by contact with the second resident stem cell population, somatic cyst stem cells (CySCs), and this involves BMP signalling. These data suggest a modified paradigm whereby the hub cells function as architects of the stem cell environment, drawing into proximity cellular components necessary for niche function. Self-renewal functions are shared by the hub cells and the CySCs. This work also reconciles key differences in GSC renewal between Drosophila testis and ovary niches, and highlights how a niche can coordinate the production of distinct lineages by having one stem cell type rely on a second. PMID: 20622868 [PubMed - as supplied by publisher] | | |
| Induced pluripotent stem cells: A new era for hepatology.
July 14, 2010 at 7:35 AM
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| | Induced pluripotent stem cells: A new era for hepatology. J Hepatol. 2010 Jun 22; Authors: Asgari S, Pournasr B, Salekdeh GH, Ghodsizadeh A, Ott M, Baharvand H Stem cell transplantation has been proposed as an attractive alternative approach to restore liver mass and function. Recent progress has been reported on the generation of induced pluripotent stem (iPS) cells from somatic cells. Human-iPS cells can be differentiated towards the hepatic lineage which presents possibilities for improving research on diseases, drug development, tissue engineering, the development of bio-artificial livers, and a foundation for producing autologous cell therapies that would avoid immune rejection and enable correction of gene defects prior to cell transplantation. This focused review will discuss how human iPS cell advances are likely to have an impact on hepatology. PMID: 20621379 [PubMed - as supplied by publisher] | | |
| A Mesenchymal-to-Epithelial Transition Initiates and Is Required for the Nuclear Reprogramming of Mouse Fibroblasts.
July 14, 2010 at 7:35 AM
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| | A Mesenchymal-to-Epithelial Transition Initiates and Is Required for the Nuclear Reprogramming of Mouse Fibroblasts. Cell Stem Cell. 2010 Jul 2;7(1):51-63 Authors: Li R, Liang J, Ni S, Zhou T, Qing X, Li H, He W, Chen J, Li F, Zhuang Q, Qin B, Xu J, Li W, Yang J, Gan Y, Qin D, Feng S, Song H, Yang D, Zhang B, Zeng L, Lai L, Esteban MA, Pei D Epithelial-to-mesenchymal transition (EMT) is a developmental process important for cell fate determination. Fibroblasts, a product of EMT, can be reset into induced pluripotent stem cells (iPSCs) via exogenous transcription factors but the underlying mechanism is unclear. Here we show that the generation of iPSCs from mouse fibroblasts requires a mesenchymal-to-epithelial transition (MET) orchestrated by suppressing pro-EMT signals from the culture medium and activating an epithelial program inside the cells. At the transcriptional level, Sox2/Oct4 suppress the EMT mediator Snail, c-Myc downregulates TGF-beta1 and TGF-beta receptor 2, and Klf4 induces epithelial genes including E-cadherin. Blocking MET impairs the reprogramming of fibroblasts whereas preventing EMT in epithelial cells cultured with serum can produce iPSCs without Klf4 and c-Myc. Our work not only establishes MET as a key cellular mechanism toward induced pluripotency, but also demonstrates iPSC generation as a cooperative process between the defined factors and the extracellular milieu. PAPERCLIP: PMID: 20621050 [PubMed - as supplied by publisher] | | |
| When Fibroblasts MET iPSCs.
July 14, 2010 at 7:35 AM
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| | When Fibroblasts MET iPSCs. Cell Stem Cell. 2010 Jul 2;7(1):5-6 Authors: Polo JM, Hochedlinger K Two independent studies by Li et al. (2010) and Samavarchi-Tehrani et al. (2010) in this issue of Cell Stem Cell suggest that a mesenchymal-to-epithelial transition is a critical initiating event during the derivation of induced pluripotent stem cells (iPSCs) from fibroblasts, indicating remarkable similarities between cellular reprogramming, development, and cancer. PMID: 20621040 [PubMed - as supplied by publisher] | | |
| Macrophages, Dendritic Cells, and Kidney Ischemia-Reperfusion Injury.
July 14, 2010 at 7:35 AM
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| | Macrophages, Dendritic Cells, and Kidney Ischemia-Reperfusion Injury. Semin Nephrol. 2010 May;30(3):268-277 Authors: Li L, Okusa MD Dendritic cells and macrophages are critical early initiators of innate immunity in the kidney and orchestrate inflammation subsequent to ischemia-reperfusion injury. They are the most abundant leukocytes present in the kidney, and they represent a heterogeneous population of cells that are capable of inducing sterile inflammation after reperfusion directly through the production of proinflammatory cytokines and other soluble inflammatory mediators or indirectly through activation of effector T lymphocytes and natural killer T cells. In addition, recent studies have indicated that kidney and immune cell micro-RNAs control gene expression and have the ability to regulate the initial inflammatory response to injury. Although dendritic cells and macrophages contribute to both innate and adaptive immunity and to injury and repair, this review focuses on the initial innate response to kidney ischemia-reperfusion injury. PMID: 20620671 [PubMed - as supplied by publisher] | | |
| Human Adipose Tissue-Derived Adult Stem Cells Can Lead to Multiorgan Engraftment.
July 14, 2010 at 7:35 AM
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| | Human Adipose Tissue-Derived Adult Stem Cells Can Lead to Multiorgan Engraftment. Transplant Proc. 2010 Jun;42(5):1849-1856 Authors: Fang B, Li Y, Song Y, Li N, Cao Y, Wei X, Lin Q, Zhao RC Recent studies have demonstrated the existence of a population of adipose tissue-derived adult stem cells that can undergo multilineage differentiation in vitro; however, it is unclear whether these cells maintain their multilineage differentiation in vivo. The objective of the present study was to examine the in vivo characteristics and behavior of a potential population of human adipose tissue-derived adult stem cells. Herein, we demonstrate that human adipose tissue-derived adult stem cells differentiate into the epithelium of the gastrointestinal tract, liver, and bronchi, and an endothelial lineage after transplantation into irradiated nonobese mice with diabetes or severe combined immunodeficiency. These findings may contribute to clinical tissue repair after injury. PMID: 20620536 [PubMed - as supplied by publisher] | | |
| Differential distribution of structural components and hydration in aortic and pulmonary heart valve conduits: Impact of detergent-based cell removal.
July 14, 2010 at 7:35 AM
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| | Differential distribution of structural components and hydration in aortic and pulmonary heart valve conduits: Impact of detergent-based cell removal. Acta Biomater. 2010 Jul 7; Authors: Naso F, Gandaglia A, Formato M, Cigliano A, Lepedda AJ, Gerosa G, Spina M Evaluation of the physiological performance of biological scaffolds for tissue-engineering applications has been mostly based on biophysical and morphological methods, with limited attention to the quantitative contribution of main structural components to native and/or treated valve assemblies. In the present study, quantization was addressed to porcine leaflet, sinus and adjacent wall of aortic and pulmonary valved conduits before and after detergent-based cell removal. Collagen, elastin, glycosaminoglycan, lipid and water contents were expressed in terms of relative concentration and volume fraction in order to assess their effective contribution to the native tissue and to changes following decellularization procedures. Main findings were recognition of unexpectedly large water and underestimated collagen content; differential distribution of elastin between the sectors and of glycosaminoglycan along the conduits; and pulmonary scaffold destabilization upon cell removal, not found in the aortic case. Simultaneous investigation allowed consistent comparison between native and decellularized tissues and added analytical knowledge crucial for designing realistic constitutive models. We have provided a quantitative structural foundation for earlier biomechanical findings in pulmonary leaflets and the basis for validation of theoretical assumptions still lacking support of experimental evidence in both conduits. Future insights into distribution of load-bearing components in human conduits are likely to provide indications important to the optimization of surgical positioning of valvular grafts. PMID: 20620247 [PubMed - as supplied by publisher] | | |
| Predicting bulk mechanical properties of cellularized collagen gels using multiphoton microscopy.
July 14, 2010 at 7:35 AM
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| | Predicting bulk mechanical properties of cellularized collagen gels using multiphoton microscopy. Acta Biomater. 2010 Jul 7; Authors: Raub C, Putnam A, Tromberg B, George SC Cellularized collagen gels are a common model in tissue engineering, but the relationship between the microstructure and bulk mechanical properties is only partially understood. Multiphoton microscopy (MPM) is an ideal non-invasive tool to examine collagen microstructure, cellularity and crosslink content in these gels. In order to identify robust image parameters that characterize microstructural determinants of the bulk elastic modulus, we performed serial MPM and mechanical tests on acellular and cellularized (normal human lung fibroblasts) collagen hydrogels, before and after glutaraldehyde crosslinking. Following gel contraction over sixteen days, cellularized collagen gel content approached that of native connective tissues ( approximately 200 mg/ml). Young's modulus (E) measurements from acellular collagen gels (range 0.5-12 kPa) exhibited a power-law concentration dependence (range 3-9 mg/ml) with exponents from 2.1-2.2, similar to other semiflexible biopolymer networks such as fibrin and actin. In contrast, cellularized collagen gel stiffness (range 0.5-27 kPa) produced concentration-dependent exponents of 0.7 uncrosslinked and 1.1 crosslinked (range approximately 5-200 mg/ml). The variation in E of cellularized collagen hydrogels can be explained by a power-law dependence on robust image parameters: either the second harmonic generation (SHG) and two-photon fluorescence (TPF) (matrix component) skewness (R(2) = 0.75, exponents of -1.0 and -0.6, respectively); or alternately the SHG and TPF (matrix component) speckle contrast (R(2) = 0.83, exponents of -0.7 and -1.8, respectively). Image parameters based on the cellular component of TPF signal did not improve the fits. The concentration dependence of E suggests enhanced stress relaxation in cellularized versus acellular gels. SHG and TPF image skewness and speckle contrast from cellularized collagen gels can predict E by capturing mechanically relevant information on collagen fiber, cell and crosslink density. PMID: 20620246 [PubMed - as supplied by publisher] | | |
| Virtual topological optimisation of scaffolds for rapid prototyping.
July 14, 2010 at 7:35 AM
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| | Virtual topological optimisation of scaffolds for rapid prototyping. Med Eng Phys. 2010 Jul 8; Authors: Almeida HD, da Silva Bártolo PJ Advanced additive techniques are now being developed to fabricate scaffolds with controlled architecture for tissue engineering. These techniques combine computer-aided design (CAD) with computer-aided manufacturing (CAM) tools to produce three-dimensional structures layer by layer in a multitude of materials. Actual prediction of the effective mechanical properties of scaffolds produced by additive technologies, is very important for tissue engineering applications. A novel computer based technique for scaffold design is topological optimisation. Topological optimisation is a form of "shape" optimisation, usually referred to as "layout" optimisation. The goal of topological optimisation is to find the best use of material for a body that is subjected to either a single load or a multiple load distribution. This paper proposes a topological optimisation scheme in order to obtain the ideal topological architectures of scaffolds, maximising its mechanical behaviour. PMID: 20620093 [PubMed - as supplied by publisher] | | |
| Cartilage repair using hyaluronan hydrogel-encapsulated human embryonic stem cell-derived chondrogenic cells.
July 14, 2010 at 7:35 AM
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| | Cartilage repair using hyaluronan hydrogel-encapsulated human embryonic stem cell-derived chondrogenic cells. Biomaterials. 2010 Sep;31(27):6968-6980 Authors: Toh WS, Lee EH, Guo XM, Chan JK, Yeow CH, Choo AB, Cao T Human embryonic stem cells (hESCs) have the potential to offer a virtually unlimited source of chondrogenic cells for use in cartilage repair and regeneration. We have recently shown that expandable chondrogenic cells can be derived from hESCs under selective growth factor-responsive conditions. In this study, we explore the potential of these hESC-derived chondrogenic cells to produce an extracellular matrix (ECM)-enriched cartilaginous tissue construct when cultured in hyaluronic acid (HA)-based hydrogel, and further investigated the long-term reparative ability of the resulting hESC-derived chondrogenic cell-engineered cartilage (HCCEC) in an osteochondral defect model. We hypothesized that HCCEC can provide a functional template capable of undergoing orderly remodeling during the repair of critical-sized osteochondral defects (1.5 mm in diameter, 1 mm depth into the subchondral bone) in a rat model. In the process of repair, we observed an orderly spatial-temporal remodeling of HCCEC over 12 weeks into osteochondral tissue, with characteristic architectural features including a hyaline-like neocartilage layer with good surface regularity and complete integration with the adjacent host cartilage and a regenerated subchondral bone. By 12 weeks, the HCCEC-regenerated osteochondral tissue resembled closely that of age-matched unoperated native control, while only fibrous tissue filled in the control defects which left empty or treated with hydrogel alone. Here we demonstrate that transplanted hESC-derived chondrogenic cells maintain long-term viability with no evidence of tumorigenicity, providing a safe, highly-efficient and practical strategy of applying hESCs for cartilage tissue engineering. PMID: 20619789 [PubMed - as supplied by publisher] | | |
| Hematopoietic Stem Cell Quiescence Promotes Error-Prone DNA Repair and Mutagenesis.
July 14, 2010 at 7:35 AM
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| | Hematopoietic Stem Cell Quiescence Promotes Error-Prone DNA Repair and Mutagenesis. Cell Stem Cell. 2010 Jul 7; Authors: Mohrin M, Bourke E, Alexander D, Warr MR, Barry-Holson K, Le Beau MM, Morrison CG, Passegué E Most adult stem cells, including hematopoietic stem cells (HSCs), are maintained in a quiescent or resting state in vivo. Quiescence is widely considered to be an essential protective mechanism for stem cells that minimizes endogenous stress caused by cellular respiration and DNA replication. We demonstrate that HSC quiescence can also have detrimental effects. We found that HSCs have unique cell-intrinsic mechanisms ensuring their survival in response to ionizing irradiation (IR), which include enhanced prosurvival gene expression and strong activation of p53-mediated DNA damage response. We show that quiescent and proliferating HSCs are equally radioprotected but use different types of DNA repair mechanisms. We describe how nonhomologous end joining (NHEJ)-mediated DNA repair in quiescent HSCs is associated with acquisition of genomic rearrangements, which can persist in vivo and contribute to hematopoietic abnormalities. Our results demonstrate that quiescence is a double-edged sword that renders HSCs intrinsically vulnerable to mutagenesis following DNA damage. PMID: 20619762 [PubMed - as supplied by publisher] | | |
| Fabrication of Functional Cardiac, Skeletal, and Smooth Muscle Pumps In Vitro.
July 14, 2010 at 7:35 AM
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| | Fabrication of Functional Cardiac, Skeletal, and Smooth Muscle Pumps In Vitro. Artif Organs. 2010 Jul 4; Authors: Evers R, Khait L, Birla RK Abstract Cardiovascular disease is one of the leading causes of death in the United States, and new treatments need to be developed in order to provide novel therapies. Tissue engineering aims to develop biologic substitutes that restore tissue function. The purpose of the current study was to construct cell-based pumps, which can be viewed as biologic left ventricular assist devices. The pumps were fabricated by culturing cardiac, skeletal, and smooth muscle cells within a fibrin gel and then each 3-D tissue construct was wrapped around a decellularized rodent aorta. We described the methodology for pump fabrication along with functional performance metric, determined by the intra-luminal pressure. In addition, histologic evaluation showed a concentric organization of components, with the muscle cells positioned on the outermost surface, followed by the fibrin gel and the decellularized aorta formed the innermost layer. Though early in development, cell-based muscle pumps have tremendous potential to be used for basic and applied research, and with further development, can be used clinically as cell-based left ventricular assist devices. PMID: 20618224 [PubMed - as supplied by publisher] | | |
| Fabricating tissue engineering scaffolds for simultaneous cell growth and drug delivery.
July 14, 2010 at 7:35 AM
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| | Fabricating tissue engineering scaffolds for simultaneous cell growth and drug delivery. Curr Pharm Des. 2010;16(21):2388-94 Authors: Chen W, Tabata Y, Tong YW The formulation and fabrication methods for several types of tissue engineering scaffolds with drug delivery capabilities are presented in this review. Tissue engineered constructs are temporary substitutes developed to treat damaged or lost tissue. One key component of such constructs is scaffolds that are often developed to mimic the extra cellular matrix (ECM). As natural ECM contains biomolecules to support proper growth and function of cells, inclusion of these biomolecular cues have been shown to be necessary for proper cell growth and function in tissue engineering. Thus, an effective tissue engineering scaffold should provide such biomolecular cues. This can be achieved through drug delivery in scaffolds. Studies have shown that drug delivery systems are necessary to protect drugs, and provide sustained drug release that is often needed for effective therapy. The tissue engineering features of 4 scaffold types are described, including films, hydrogels, fibers, and microspheres/nanospheres. Fabrication techniques and drug encapsulation methods for these scaffolds are reviewed in addition to some observations arising from the use of these techniques and methods. PMID: 20618159 [PubMed - in process] | | |
| EFFECT OF PI3K, ERK1/2 AND P38 MAPK INHIBITION ON OSTEOGENIC DIFFERENTIATION OF MUSCLE-DERIVED STEM CELLS.
July 14, 2010 at 7:35 AM
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| | EFFECT OF PI3K, ERK1/2 AND P38 MAPK INHIBITION ON OSTEOGENIC DIFFERENTIATION OF MUSCLE-DERIVED STEM CELLS. Tissue Eng Part A. 2010 Jul 9; Authors: Payne KA, Meszaros LB, Phillippi JA, Huard J Skeletal muscle-derived stem cells (MDSCs) can undergo osteogenesis when treated with bone morphogenetic proteins (BMPs), making them a potential cell source for bone tissue engineering. The signaling pathways that regulate BMP4-induced osteogenesis in MDSCs are not well understood, although they may provide a means to better regulate differentiation during bone regeneration. The objective of this study was to characterize the signaling pathways involved in the BMP4-induced osteogenesis of MDSCs. Cells were treated with BMP4 and specific inhibitors to the ERK1/2, p38 MAPK and PI3K pathways (PD98059, SB203580 and Ly294002, respectively). Cellular proliferation, expression of osteoblast-related genes, alkaline phosphatase (ALP) activity, and tissue mineralization were measured to determine the role of each pathway in the osteogenic differentiation of MDSCs. Inhibition of the ERK1/2 pathway increased ALP activity and mineralization, while inhibition of the p38 MAPK pathway decreased osteogenesis, suggesting opposing roles of these pathways in the BMP4-induced osteogenesis of MDSCs. Inhibition of the PI3K pathway significantly increased mineralization by MDSCs. These findings highlight the involvement of the ERK1/2, p38 MAPK and PI3K pathways in opposing capacities in MDSC differentiation and warrant further investigation, as it may identify novel therapeutic targets for the development of stem cell-based therapies for bone tissue engineering. PMID: 20617875 [PubMed - as supplied by publisher] | | |
| A novel vascularized patch enhances cell survival and modifies ventricular remodeling in a rat myocardial infarction model.
July 14, 2010 at 2:35 AM
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| | A novel vascularized patch enhances cell survival and modifies ventricular remodeling in a rat myocardial infarction model. J Thorac Cardiovasc Surg. 2010 Jul 8; Authors: Zhou Q, Zhou JY, Zheng Z, Zhang H, Hu SS OBJECTIVE: Although stem cells hold a great therapeutic potential for injured tissues, limited survival of transplanted stem cells has hindered the clinical application of this technology. We hypothesized that an omentum-based stem cell-supporting patch could provide adequate nutrients and microenvironment to prolong cell survival. We examined this hypothesis in rats with experimental myocardial infarction. METHODS: The omentum-based supporting patch was constructed by stitching polylactic acid-co-glycolic acid polymer seeded with mesenchymal stem cells from male Sprague-Dawley rats. Eight weeks after the experimental myocardial infarction, which was created by ligating the left coronary artery of female Sprague-Dawley rats, mesenchymal stem cells were transplanted with (n = 16) or without (n = 14) the supporting patch. After 4 weeks, transplanted mesenchymal stem cell survival, ventricular remodeling, and cardiac performance were examined. RESULTS: Significantly more cells survived after 4 weeks in rats transplanted with mesenchymal stem cells on the supporting patch assessed by means of polymerase chain reaction detection of the Sry gene than seen in those without the supporting patch (2.61 +/- 0.40 vs 1.19 +/- 0.12, P < .05). Rats with myocardial infarction that received mesenchymal stem cells with the patch also had significantly improved ventricular remodeling and cardiac function than those without the patch. Wrapping infarcted myocardium with omentum alone did not change the myocardial function. CONCLUSIONS: The omentum-based cell-supporting patch provided a favorable microenvironment for transplanted mesenchymal stem cell survival, which resulted in favorable ventricular remodeling and restoration of cardiac function in rats with experimental myocardial infarction. Further validation of the technique in human subjects could make mesenchymal stem cell transplantation a viable therapeutic option for patients with cardiac disease. PMID: 20619860 [PubMed - as supplied by publisher] | | | | 
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