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| Extrinsic regulation of pluripotent stem cells.
June 11, 2010 at 6:49 AM
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| | Extrinsic regulation of pluripotent stem cells. Nature. 2010 Jun 10;465(7299):713-20 Authors: Pera MF, Tam PP During early mammalian development, as the pluripotent cells that give rise to all of the tissues of the body proliferate and expand in number, they pass through transition states marked by a stepwise restriction in developmental potential and by changes in the expression of key regulatory genes. Recent findings show that cultured stem-cell lines derived from different stages of mouse development can mimic these transition states. They further reveal that there is a high degree of heterogeneity and plasticity in pluripotent populations in vitro and that these properties are modulated by extrinsic signalling. Understanding the extrinsic control of plasticity will guide efforts to use human pluripotent stem cells in research and therapy. PMID: 20535200 [PubMed - in process] | | |
| Stem Cell Quiescence in the Hippocampal Neurogenic Niche Is Associated With Elevated Transforming Growth Factor-beta Signaling in an Animal Model of Huntington Disease.
June 11, 2010 at 6:49 AM
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| | Stem Cell Quiescence in the Hippocampal Neurogenic Niche Is Associated With Elevated Transforming Growth Factor-beta Signaling in an Animal Model of Huntington Disease. J Neuropathol Exp Neurol. 2010 Jun 8; Authors: Kandasamy M, Couillard-Despres S, Raber KA, Stephan M, Lehner B, Winner B, Kohl Z, Rivera FJ, Nguyen HP, Riess O, Bogdahn U, Winkler J, von Hörsten S, Aigner L Cellular proliferation, differentiation, integration, and survival within the adult neural stem cell niche are altered under pathological conditions, but the molecular cues regulating the biology of this niche are mostly unknown. We examined the hippocampal neural stem cell niche in a transgenic rat model of Huntington disease. In this model, progressive cognitive deficits develop at the age of 9 months, suggesting possible hippocampal dysfunction. We found adisease-associated progressive decline in hippocampal progenitorcell proliferation accompanied by an expansion of the pool of 5-bromo-2-deoxyuridine label-retaining Sox-2-positive quiescent stem cells in the transgenic animals. Increments in quiescent stem cells occurred at the expense of cAMP-responsive element-binding protein-mediated neuronal differentiation and survival. Because elevated levels of transforming growth factor-beta1 (TGF-beta1) impair neural progenitor proliferation, we investigated hippocampal TGF-beta signaling and determined that TGF-beta1 induces the neural progenitorsto exit the cell cycle. Although phospho-Smad2, an effector of TGF-beta signaling, is normally absent in subgranular stem cells, it accumulated progressively in Sox2/glial fibrillary acidic protein-expressing cells of the subgranular zone in the transgenic rats. These results indicate that alterations in neurogenesis in transgenic Huntington disease rats occur in successive phases that are associated with increasing TGF-beta signaling. Thus, TGF-beta1 signaling seems to be a crucial modulator of neurogenesis in Huntington disease and may represent a target for future therapy. PMID: 20535034 [PubMed - as supplied by publisher] | | |
| Fibroblast-secreted hepatocyte growth factor plays a functional role in esophageal squamous cell carcinoma invasion.
June 11, 2010 at 6:49 AM
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| | Fibroblast-secreted hepatocyte growth factor plays a functional role in esophageal squamous cell carcinoma invasion. Proc Natl Acad Sci U S A. 2010 Jun 1; Authors: Grugan KD, Miller CG, Yao Y, Michaylira CZ, Ohashi S, Klein-Szanto AJ, Diehl JA, Herlyn M, Han M, Nakagawa H, Rustgi AK Squamous cell cancers comprise the most common type of human epithelial cancers. One subtype, esophageal squamous cell carcinoma (ESCC), is an aggressive cancer with poor prognosis due to late diagnosis and metastasis. Factors derived from the extracellular matrix (ECM) create an environment conducive to tumor growth and invasion. Specialized cancer-associated fibroblasts (CAFs) in the ECM influence tumorigenesis. We have shown previously that the nature and activation state of fibroblasts are critical in modulating the invasive ability of ESCC in an in vivo-like organotypic 3D cell culture, a form of human tissue engineering. Dramatic differences in invasion of transformed esophageal epithelial cells depended on the type of fibroblast in the matrix. We hypothesize that CAFs create an environment primed for growth and invasion through the secretion of factors. We find that fibroblast secretion of hepatocyte growth factor (HGF) fosters the ability of transformed esophageal epithelial cells to invade into the ECM, although other unidentified factors may cooperate with HGF. Genetic modifications of both HGF in fibroblasts and its receptor Met in epithelial cells, along with pharmacologic inhibition of HGF and Met, underscore the importance of this pathway in ESCC invasion and progression. Furthermore, Met activation is increased upon combinatorial overexpression of epidermal growth factor receptor (EGFR) and p53(R175H), two common genetic mutations in ESCC. These results highlight the potential benefit of the therapeutic targeting of HGF/Met signaling in ESCC and potentially other squamous cancers where this pathway is deregulated. PMID: 20534479 [PubMed - as supplied by publisher] | | |
| Regenerative Medicine Applied to Solid Organ Transplantation: Where Do We Stand?
June 11, 2010 at 6:49 AM
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| | Regenerative Medicine Applied to Solid Organ Transplantation: Where Do We Stand? Transplant Proc. 2010 May;42(4):1011-1013 Authors: Orlando G, Di Cocco P, D'Angelo M, Clemente K, Famulari A, Pisani F The objective of regenerative medicine (RM) and Tissue Engineering (TE) is to create living functional tissues to repair or replace tissues or organ functions. This field holds the promise of regenerating damaged tissues and organs in the body. It has the potential to solve the problems of organ shortage and of toxicities deriving from life-long immunosuppression. In fact, cells in the regenerated organ would match those of the patient, from whom they would normally be derived. In the past decade, RM/TE has achieved striking results which are of interest to the transplant community. However, major roadblocks on the avenue to full success include the need for a deeper understanding of cell biology and of interactions with the extracellular matrix. We are presently not able to grow and expand cells indefinitely and safely in various scenarios where RM/TE may be indicated. The production of adequately vascularized scaffolds to optimize nutrients and oxygen delivery, assessment of the viability and function of the cells in the bioengineered construct, and the costs remain areas of scientific research. PMID: 20534211 [PubMed - as supplied by publisher] | | |
| Synthesis, Characterization and Drug Release of Biocompatible/Biodegradable Non-toxic Poly(urethane urea)s Based on Poly(epsilon-caprolactone)s and Lysine-Based Diisocyanate.
June 11, 2010 at 6:49 AM
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| | Synthesis, Characterization and Drug Release of Biocompatible/Biodegradable Non-toxic Poly(urethane urea)s Based on Poly(epsilon-caprolactone)s and Lysine-Based Diisocyanate. J Biomater Sci Polym Ed. 2010 Jun 8; Authors: Reddy TT, Kano A, Maruyama A, Takahara A Segmented poly(urethane urea)s (SPUUs) based on aliphatic diisocyanato (2,6-diisocyanato methyl caproate (lysine-based diisocyanate, LDI)), poly(epsilon-caprolactone diol)s (PCLs) with molecular weights 530, 1250 and 2000, and 1,4-butanediamine were synthesized in absence of catalyst. The resulting SPUUs, with different soft segment length, were characterized by suitable analytical techniques. The synthesized SPUUs had high molecular weights, low glass-transition temperatures (</=-15 degrees C) and high elongation-at-break. The degradation of SPUUs in alkaline solution and in vitro drug release of sulfamethoxazole in pH 7.4 buffer were investigated. In addition, the degradation behavior of PCL1250-based SPUU was investigated by exposing to a buffer solution and biochemical oxygen demand (BOD) tests in an activated sludge. The drug release data was analyzed by an empirical equation ((M(t)/M(infinity))=kt(n)). Finally, NIH3T3 fibroblasts have been used for cell-adhesion studies on these materials to investigate the biocompatibility. The synthesized SPUUs combine physical and bioresponsive and biodegradable properties that might be employed in wound dressing, drug delivery and tissue-engineering applications. PMID: 20534197 [PubMed - as supplied by publisher] | | |
| Characterization of Poly(epsilon-caprolactone)/Polyfumarate Blends as Scaffolds for Bone Tissue Engineering.
June 11, 2010 at 6:49 AM
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| | Characterization of Poly(epsilon-caprolactone)/Polyfumarate Blends as Scaffolds for Bone Tissue Engineering. J Biomater Sci Polym Ed. 2010 Jun 8; Authors: Fernandez JM, Molinuevo MS, Cortizo AM, McCarthy AD, Cortizo MS There is considerable interest in the design of polymeric biomaterials that can be used for the repair of bone defects. In this study, we used ultrasound to prepare a compatibilized blend of poly(epsilon-caprolactone) (PCL) and poly(diisopropyl fumarate) (PDIPF). The formation of post-sonication inter-polymer coupling products was verified by SEC analysis of a blend with azo-labeled PDIPF. We also analyzed the physicochemical and mechanical properties of the compatibilized blend. When compared to PCL alone, the PCL/PDIPF blend showed no difference in its resistance as evaluated by the elastic modulus, although it did show a 50% decrease in ultimate tensile stress (P<0.05) and an 84% decrease in elongation-at-break (P<0.05). However, the mechanical properties of this blend were comparable to those of trabecular bone. We next evaluated biocompatibility of the PCL/PDIPF blend, and of homo-polymeric PCL and PDIPF films for comparison, with UMR106 and MC3T3E1 osteoblastic cells. Osteoblasts plated on the compatibilized blend adhered and proliferated more than on either homo-polymer, showed a greater number of cellular processes with a better organized actin cytoskeleton and expressed more type-I collagen and mineral, both markers of osteoblast phenotype. These results support the hypothesis that this new compatibilized blend could be useful in future applications for bone regeneration. PMID: 20534186 [PubMed - as supplied by publisher] | | |
| Electrospun Scaffolds of a Polyhydroxyalkanoate Consisting of omega-Hydroxylpentadecanoate Repeat Units: Fabrication and in Vitro Biocompatibility Studies.
June 11, 2010 at 6:49 AM
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| | Electrospun Scaffolds of a Polyhydroxyalkanoate Consisting of omega-Hydroxylpentadecanoate Repeat Units: Fabrication and in Vitro Biocompatibility Studies. J Biomater Sci Polym Ed. 2010 Jun 8; Authors: Focarete ML, Gualandi C, Scandola M, Govoni M, Giordano E, Foroni L, Valente S, Pasquinelli G, Gao W, Gross RA Electrospinning was used to fabricate fibrous scaffolds of lipase-catalyzed poly(omega-pentadecalactone) (PPDL). The slow resorbability of this biomaterial is expected to be valuable for tissue-engineering applications requiring long healing times. The effect of solvent systems and instrumental parameters on fiber morphology was investigated. PPDL electrospinning was optimized and defect-free fibers (diameter 410 +/- 150 nm) were obtained by using a mixed three-solvent system. Scaffolds were characterized by scanning electron microscopy, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and wide angle X-ray diffraction (WAXS). TGA showed no residual solvent in the scaffolds. DSC and WAXS results indicated that electrospun PPDL is semicrystalline. Biocompatibility of PPDL scaffolds was evaluated through indirect cytotoxicity tests using embryonic rat cardiac H9c2 cells. The ability of PPDL electrospun mats to support cell growth was verified by culturing H9c2 cells onto the scaffold. Cell adhesion, proliferation and morphology were evaluated. The results indicated that PPDL mats are not cytotoxic and they support proliferation of H9c2 cells. The cumulative results of this study suggest further exploration of PPDL fibrous mats as scaffolds for tissue-engineered constructs. PMID: 20534185 [PubMed - as supplied by publisher] | | |
| Bioengineering strategies for regeneration of craniofacial bone: a review of emerging technologies.
June 11, 2010 at 6:49 AM
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| | Bioengineering strategies for regeneration of craniofacial bone: a review of emerging technologies. Oral Dis. 2010 May 30; Authors: Ward BB, Brown SE, Krebsbach PH Oral Diseases (2010) DOI: 10.1111/j.1601-0825.2010.01682.x Although advances in surgical techniques and bone grafting have significantly improved the functional and cosmetic restoration of craniofacial structures lost because of trauma or disease, there are still significant limitations in our ability to regenerate these tissues. The regeneration of oral and craniofacial tissues presents a formidable challenge that requires synthesis of basic science, clinical science, and engineering technology. Tissue engineering is an interdisciplinary field of study that addresses this challenge by applying the principles of engineering to biology and medicine toward the development of biological substitutes that restore, maintain, and improve normal function. This review will explore the impact of biomaterials design, stem cell biology and gene therapy on craniofacial tissue engineering. PMID: 20534013 [PubMed - as supplied by publisher] | | |
| The potential role of metal ion release as a marker of loosening in patients with total knee replacement: a cohort study.
June 11, 2010 at 6:49 AM
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| | The potential role of metal ion release as a marker of loosening in patients with total knee replacement: a cohort study. J Bone Joint Surg Br. 2010 May;92(5):634-8 Authors: Savarino L, Tigani D, Greco M, Baldini N, Giunti A We investigated the role of ion release in the assessment of fixation of the implant after total knee replacement and hypothesised that ion monitoring could be a useful parameter in the diagnosis of prosthetic loosening. We enrolled 59 patients with unilateral procedures and measured their serum aluminium, titanium, chromium and cobalt ion levels, blinded to the clinical and radiological outcome which was considered to be the reference standard. The cut-off levels for detection of the ions were obtained by measuring the levels in 41 healthy blood donors who had no implants. Based on the clinical and radiological evaluation the patients were divided into two groups with either stable (n = 24) or loosened (n = 35) implants. A significant increase in the mean level of Cr ions was seen in the group with failed implants (p = 0.001). The diagnostic accuracy was 71% providing strong evidence of failure when the level of Cr ions exceeded the cut-off value. The possibility of distinguishing loosening from other causes of failure was demonstrated by the higher diagnostic accuracy of 83%, when considering only patients with failure attributable to loosening. Measurement of the serum level of Cr ions may be of value for detecting failure due to loosening when the diagnosis is in doubt. The other metal ions studies did not have any diagnostic value. PMID: 20435998 [PubMed - indexed for MEDLINE] | | |
| Too friable to treat?
June 11, 2010 at 6:49 AM
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| | Too friable to treat? Lancet. 2010 May 1;375(9725):1578 Authors: Kimura K, Sakai-Kimura M, Takahashi R, Watanabe A, Mukai M, Noma S, Fukuda K PMID: 20435230 [PubMed - indexed for MEDLINE] | | |
| Potential role of tartrate-resistant acid phosphatase 5b (TRACP 5b) as a surrogate marker of late loosening in patients with total hip arthroplasty: a cohort study.
June 11, 2010 at 6:49 AM
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| | Potential role of tartrate-resistant acid phosphatase 5b (TRACP 5b) as a surrogate marker of late loosening in patients with total hip arthroplasty: a cohort study. J Orthop Res. 2010 Jul;28(7):887-92 Authors: Savarino L, Avnet S, Greco M, Giunti A, Baldini N In a cohort study, the role of the active tartrate-resistant acid phosphatase (TRACP 5b), a marker of bone-resorbing osteoclasts, for the assessment of loosening after total hip arthroplasty (THA), was analyzed, as well as its correlation with osteolysis and multinucleated cell appearance in the retrievals. Eighty THA patients, who went consecutively to the orthopedic department, were asked to participate, and 54 accepted and were enrolled in the study. Finally, 46 subjects were analyzed, clinical-radiographic evaluation was considered the gold standard, serum TRACP 5b was blindly measured, and a cut-off was obtained, by performing a ROC Curve. Based on the gold standard, patients were split by 19 stable and 27 loosened subjects, and results were matched. TRACP 5b was significantly higher in loosened patients than in stable ones (p < 0.001). A good specificity (89.5%), positive predictive value (90.0%), and likelihood ratio (6.33) were calculated, that provided strong evidence of loosening with TRACP 5b levels higher than the cut-off. Moreover, TRACP 5b and osteolysis (Fisher's exact test, p = 0.03) were found significantly correlated. TRACP 5b has been proven a reliable marker, specifically related to resorbing-multinucleated cells, to ascertain late loosening in THA, and could support standard procedures, if confirmed by performing prospective studies. PMID: 20063383 [PubMed - indexed for MEDLINE] | | |
| The delayed repair of sciatic nerve defects with tissue-engineered nerve grafts in rats.
June 11, 2010 at 6:49 AM
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| | The delayed repair of sciatic nerve defects with tissue-engineered nerve grafts in rats. Artif Cells Blood Substit Immobil Biotechnol. 2010;38(1):29-37 Authors: Shi W, Yao J, Chen X, Lin W, Gu X, Wang X The purpose of this study was to evaluate the feasibility of using tissue-engineered nerve grafts for delayed repair of peripheral nerve defects. A 1-month delayed, 10-mm long sciatic nerve defect was created for rats, which were divided into three grafted groups and a non-grafted group. For bridging the nerve defects, the rats in three grafted groups were subjected to surgical repair with tissue-engineered nerve grafts made of a chitosan/polyglycolic acid (PGA) conduit filled with neural stem cells (NSCs), chitosan/PGA conduits, and autologous nerve grafts, respectively. At 3 months after nerve grafting, the data from electrophysiology, retrograde tracing and histological investigation revealed that the better outcomes in sciatic nerve regeneration and target muscle re-innervation were achieved in three grafted groups as compared to those in non-grafted group without major differences between three grafted groups. Our results suggest that grafting of chitosan/PGA conduits might be a promising technique for repairing peripheral nerve injuries after a 1-month delay, while introduction of NSCs seem to show no significant additional benefits to regenerative outcomes. PMID: 20047519 [PubMed - indexed for MEDLINE] | | |
| The regenerative effect of platelet-rich plasma on healing in large osteochondral defects.
June 11, 2010 at 6:49 AM
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| | The regenerative effect of platelet-rich plasma on healing in large osteochondral defects. Int Orthop. 2010 Apr;34(4):589-97 Authors: Sun Y, Feng Y, Zhang CQ, Chen SB, Cheng XG Platelet-rich plasma (PRP), a platelet concentrate made of autogenous blood, has been used to improve bone and soft tissue defect healing in recent years. The aim of this study was to assess the effect of PRP on articular cartilage defects in a rabbit model. Forty-eight osteochondral defects created in the femoropatellar groove were (a) left untreated, (b) treated with autogenous PRP in a poly-lactic-glycolic acid (PLGA), or (c) with PLGA alone. Platelets were enriched 5.12-fold compared to normal blood in the PRP. After four and 12 weeks, the explanted tissue specimens were assessed by macroscopic examination, micro-computed tomography, and histological evaluation. Macroscopic examination, micro-computed tomography and histology of the newly formed cartilage and bone in the defect differ significantly between the PRP-treated and the untreated groups, and stimulatory effect of PRP on osteochondral formation was observed. In conclusion, PRP in PLGA improves osteochondral healing in a rabbit model. PMID: 19434411 [PubMed - indexed for MEDLINE] | | |
| Collagen gel coating or cyclosporine A for improving histocompatibility of chicken calamus keratin.
June 11, 2010 at 6:49 AM
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| | Collagen gel coating or cyclosporine A for improving histocompatibility of chicken calamus keratin. Nan Fang Yi Ke Da Xue Xue Bao. 2007 Jun;27(6):751-5 Authors: Dong WR, Qiu XX, Zhao BL, Chen YH, Xiao YQ, Guo JS, Zou ZZ OBJECTIVE: To improve the histocompatibility of chicken calamus keratin (CCK) graft by collagen-gel coating or using of cyclosporine A (CsA). METHODS: Thirty SD rats were equally randomized into 5 groups, and in 4 of them, CCK implantation into the bilateral erector spinae was performed on different treatment protocols. In group A, the rats received daily intraperitoneal injection of CsA (5 mg/kg) for two consecutive weeks after CCK implantation; in group B, CCK was soaked in CsA (2.5 mg/ml) solution at 4 degrees Celsius; for 48 h before grafting; in group C, CCK coated with collagen gel was grafted; and in group D, only CCK was implanted. Rats in the fifth group received only cutaneous incision as well as muscular dissection to serve as the blank control. CCK degradation and its effect on the surrounding tissues were observed at 2, 4 and 8 weeks after grafting. Immunohistochemistry was performed to identify T lymphocyte infiltration in the host tissues. RESULTS: All the rats survived the operation. Numerous macrophages, especially multinucleated giant cells occurred on the peripheral of the CCK grafts, and small degraded CCK pieces were observed in their cytoplasm. Only a few inflammatory cells were seen in the host tissues. At 2, 4 and 8 weeks after CCK implantation, only a few CD3-positive cells were found in all the groups, and in group A and B, the density of T lymphocytes was significantly lower than that in group D, and there was no significant difference between group A and the blank control group. CONCLUSIONS: CsA significantly improves the histocompatibility of CCK material, and short-term systemic CsA administration achieves the best results. Macrophages, especially multinucleated giant cells participate in CCK degradation in vivo. PMID: 17584631 [PubMed - indexed for MEDLINE] | | | | 
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