| NHLBI to convene symposium on cardiovascular regenerative medicine
October 8, 2009 at 7:59 pm
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| Tendon, ligament repair in horses focus of research
October 8, 2009 at 4:51 pm
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| NHLBI supports consortium exploring stem-cell-based tools and treatments
October 8, 2009 at 3:51 pm
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| Governor recognizes stem cell research at Einstein
October 8, 2009 at 3:51 pm
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| Stem cell therapy with overexpressed VEGF and PDGF genes improves cardiac function in a rat infarct model.
October 8, 2009 at 8:39 am
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| | Stem cell therapy with overexpressed VEGF and PDGF genes improves cardiac function in a rat infarct model. PLoS One. 2009;4(10):e7325 Authors: Das H, George JC, Joseph M, Das M, Abdulhameed N, Blitz A, Khan M, Sakthivel R, Mao HQ, Hoit BD, Kuppusamy P, Pompili VJ BACKGROUND: Therapeutic potential was evaluated in a rat model of myocardial infarction using nanofiber-expanded human cord blood derived hematopoietic stem cells (CD133+/CD34+) genetically modified with VEGF plus PDGF genes (VIP). METHODS AND FINDINGS: Myocardial function was monitored every two weeks up to six weeks after therapy. Echocardiography revealed time dependent improvement of left ventricular function evaluated by M-mode, fractional shortening, anterior wall tissue velocity, wall motion score index, strain and strain rate in animals treated with VEGF plus PDGF overexpressed stem cells (VIP) compared to nanofiber expanded cells (Exp), freshly isolated cells (FCB) or media control (Media). Improvement observed was as follows: VIP>Exp> FCB>media. Similar trend was noticed in the exercise capacity of rats on a treadmill. These findings correlated with significantly increased neovascularization in ischemic tissue and markedly reduced infarct area in animals in the VIP group. Stem cells in addition to their usual homing sites such as lung, spleen, bone marrow and liver, also migrated to sites of myocardial ischemia. The improvement of cardiac function correlated with expression of heart tissue connexin 43, a gap junctional protein, and heart tissue angiogenesis related protein molecules like VEGF, pNOS3, NOS2 and GSK3. There was no evidence of upregulation in the molecules of oncogenic potential in genetically modified or other stem cell therapy groups. CONCLUSION: Regenerative therapy using nanofiber-expanded hematopoietic stem cells with overexpression of VEGF and PDGF has a favorable impact on the improvement of rat myocardial function accompanied by upregulation of tissue connexin 43 and pro-angiogenic molecules after infarction. PMID: 19809493 [PubMed - in process] |
| Are stem cells a cure for diabetes?
October 8, 2009 at 8:39 am
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| | Are stem cells a cure for diabetes? Clin Sci (Lond). 2010 Jan;118(2):87-97 Authors: McCall MD, Toso C, Baetge EE, Shapiro AM With the already heightened demand placed on organ donation, stem cell therapy has become a tantalizing idea to provide glucose-responsive insulin-producing cells to Type 1 diabetic patients as an alternative to islet transplantation. Multiple groups have developed varied approaches to create a population of cells with the appropriate characteristics. Both adult and embryonic stem cells have received an enormous amount of attention as possible sources of insulin-producing cells. Although adult stem cells lack the pluripotent nature of their embryonic counterparts, they appear to avoid the ethical debate that has centred around the latter. This may limit the eventual application of embryonic stem cells, which have already shown promise in early mouse models. One must also consider the potential of stem cells to form teratomas, a complication which would prove devastating in an immunologically compromised transplant recipient. The present review looks at the progress to date in both the adult and embryonic stem cells fields as potential treatments for diabetes. We also consider some of the limitations of stem cell therapy and the potential complications that may develop with their use. PMID: 19807695 [PubMed - in process] |
| Learning to perform ear reconstruction.
October 8, 2009 at 7:17 am
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| | Learning to perform ear reconstruction. Facial Plast Surg. 2009 Aug;25(3):158-63 Authors: Wilkes GH Learning how to perform ear reconstruction is very difficult. There are no standardized teaching methods. This has resulted in many ear reconstructions being suboptimal. Learning requires a major commitment by the surgeon. Factors to be seriously considered by those considering performing this surgery are (1) commitment, (2) aptitude, (3) training methods available, (4) surgical skills and experience, and (5) additional equipment needs. Unless all these factors are addressed in a surgeon's decision to perform this form of reconstruction, the end result will be compromised, and patient care will not be optimized. It is hoped that considering these factors and following this approach will result in a higher quality of aesthetic result. The future of ear reconstruction lies in the use of advanced digital technologies and tissue engineering. PMID: 19809946 [PubMed - in process] |
| Mineral status and mechanical properties of cancellous bone exposed to hydrogen peroxide for various time periods.
October 8, 2009 at 7:17 am
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| | Mineral status and mechanical properties of cancellous bone exposed to hydrogen peroxide for various time periods. Cell Tissue Bank. 2009 Oct 7; Authors: Li D, Bi L, Meng G, Wang J, Lv R, Liu M, Liu J, Hu Y Processed cancellous bone has been regarded as one alternative for the treatment of bone defects. In order to avoid immunogenic effects and preserve the natural properties of the bone, the optimal processing method should be determined. To observe the influence of hydrogen peroxide on the mineral status and mechanical properties of cancellous bone for various time periods and find the optimal processing time. Cancellous bone granules from bovine femur condyles were treated with 30% hydrogen dioxide for 0, 12, 24, 36, 48, 60 and 72 h separately. The microstructure and mineral content of the granules were evaluated by ash analysis, Micro-CT, scanning electron micrograph and energy dispersive X-ray. The biomechanical properties were analyzed by applying cranial-caudal compression in a materials testing machine. With increasing exposure to hydrogen peroxide, the BMD and BMC of granules gradually decreased, and the Ca/P molar ratios clearly increased (P < 0.05). Meanwhile, the mineral content of the granules increased from 48.5 +/- 1.3 to 79.5 +/- 2.1%. Substantial decreases in the strength of the granules were observed, and after 48 h severe decreases were noted. The decrease in strength was also evident after normalizing the parameters to the cross-sectional area. Granules of bovine cancellous bone matrix should be processed by hydrogen peroxide for 12 to 36 h to fulfill the basic requirements of a bone tissue engineering scaffold. These granules could potentially be useful during orthopedic operations. PMID: 19809891 [PubMed - as supplied by publisher] |
| Culturing of ventricle cells at high density and construction of engineered cardiac cell sheets without scaffold.
October 8, 2009 at 7:17 am
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| | Culturing of ventricle cells at high density and construction of engineered cardiac cell sheets without scaffold. Int Heart J. 2009 Sep;50(5):653-62 Authors: Guo Y, Zhang XZ, Wei Y, Guo C, Li RX, Zeng QC, Zhang YJ In natural heart tissue, cell density is about 1.0 x 108/cm(3), and the cell metabolism is very active. Therefore, culturing heart cells in 3-dimensions at high density and construction of engineered cardiac tissue in vitro is very difficult. The aim of this study was to simulate 3-dimensional culturing of cardiac cells and pursue a novel method to construct engineered cardiac tissue in vitro. The isolated neonatal rat ventricle cells were cultured at a high seeding density of 1 x 10(6)/cm(2). The cells at high density metabolized actively; the glucose consumption and lactic acid production of ventricle cells were much greater than those of fibroblasts cultured at the same density. The pH value of the culture medium of ventricle cells consistently decreased more rapidly. These cultured ventricle cells contained vascular endothelial cells, cardiomyocytes, and smooth muscle cells that appeared close to each other, and had overlapping nuclei and plenty of extracellular collagen. The cells at high density were treated with 0.2% trypsin to construct engineered cardiac cell sheets without scaffold. The engineered cardiac cell sheets could beat and roll up spontaneously, each sheet was 3 to 5 cells thick, and contained abundant cardiomyocytes and extracellular collagen.In conclusion, cells cultured at high-density in vitro grew well in a 2-dimensional culturing environment, formed "quasi 3-dimension" culturing, and engineered cardiac cell sheets comprised of several layers of cells were constructed. This study provides some guidance for cardiac tissue engineering and a novel method to construct engineered cardiac tissue without scaffold. PMID: 19809213 [PubMed - in process] |
| Bone Regeneration Using an Acellular Extracellular Matrix and Bone Marrow Mesenchymal Stem Cells Expressing Cbfa1.
October 8, 2009 at 7:17 am
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| | Bone Regeneration Using an Acellular Extracellular Matrix and Bone Marrow Mesenchymal Stem Cells Expressing Cbfa1. Biosci Biotechnol Biochem. 2009 Oct 7; Authors: Dong SW, Ying DJ, Duan XJ, Xie Z, Yu ZJ, Zhu CH, Yang B, Sun JS To treat bone defects, tissue-engineering methods combine an appropriate scaffold with cells and osteogenic signals to stimulate bone repair. Mesenchymal stem cells (MSCs) derived from adult bone marrow are an ideal source of cells for tissue engineering, in particular for applications in skeletal and hard tissue repair. Core binding factor alpha1 (Cbfa1) is an essential transcription factor for osteoblast differentiation. However, the effects of Cbfa1 on MSCs in vitro and in vivo have not been well characterized. In this study, we found that MSCs modified genetically to express Cbfa1 promoted the healing of segmental defects of the radius in rabbits. First, osteogenic differentiation of MSCs transfected with an adenovirus encoding Cbfa1 was demonstrated. Expression of mRNA from a number of osteoblastic marker genes, including osteocalcin, osteopontin, and type I collagen, was detected. In addition, alkaline phosphatase activity and increased osteocalcin content were observed. The cells expressing the Cbfa1 gene were then combined with acellular bone extracellular matrix in a flow perfusion culture system. Finally, the cell-matrix constructs were implanted into radius defects in the rabbit model. After 12 weeks, radiographic, histological, and biomechanical analyses showed that MSCs modified with the Cbfa1 gene resulted in a significantly higher amount of newly-formed bone and rebuilding of the marrow cavity than control cell-matrix constructs. This study indicates that MSCs modified with the Cbfa1 gene can act as suitable seed cells for the regeneration of bone defects. PMID: 19809195 [PubMed - as supplied by publisher] |
| Age-Related Changes in Pericellular Hyaluronan Organization Leads to Impaired Dermal Fibroblast to Myofibroblast Differentiation.
October 8, 2009 at 7:17 am
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| | Age-Related Changes in Pericellular Hyaluronan Organization Leads to Impaired Dermal Fibroblast to Myofibroblast Differentiation. Am J Pathol. 2009 Oct 1; Authors: Simpson RM, Meran S, Thomas D, Stephens P, Bowen T, Steadman R, Phillips A We have previously demonstrated that transforming growth factor-beta1 (TGF-beta1)-mediated fibroblast-myofibroblast differentiation is associated with accumulation of a hyaluronan (HA) pericellular coat. The current study demonstrates failure of fibroblast-myofibroblast differentiation associated with in vitro aging. This is associated with attenuation of numerous TGF-beta1-dependent responses, including HA synthesis and induction of the HA synthase enzyme HAS2 and the hyaladherin tumor necrosis factor-alpha-stimulated gene 6 (TSG-6), which led to an age-related defect in pericellular HA coat assembly. Inhibition of HAS2-dependent HA synthesis by gene silencing, removal of the HA coat by hyaluronidase digestion, or gene silencing of TSG-6 or cell surface receptor CD44 led to abrogation of TGF-beta1-dependent induction of alpha-smooth muscle actin in "young" cells. This result supports the importance of HAS2-dependent HA synthesis and the HA coat during phenotypic activation. Interleukin-1beta stimulation, however, failed to promote phenotypic conversion despite coat formation. A return to basal levels of HA synthesis in aged cells by HAS2 overexpression restored TGF-beta1-dependent induction of TSG-6 and pericellular HA coat assembly. However, this did not lead to the acquisition of a myofibroblast phenotype. Coordinated induction of HAS2 and TSG-6 facilitation of pericellular HA coat assembly is necessary for TGF-beta1-dependent activation of fibroblasts, and both components of this response are impaired with in vitro aging. In conclusion, the HA pericellular coat is integral but not sufficient to correct for the age-dependent defect in phenotypic conversion. PMID: 19808648 [PubMed - as supplied by publisher] |
| Hybrid cellular automaton modeling of nutrient modulated cell growth in tissue engineering constructs.
October 8, 2009 at 7:17 am
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| | Hybrid cellular automaton modeling of nutrient modulated cell growth in tissue engineering constructs. J Theor Biol. 2009 Oct 3; Authors: Chung CA, Lin TH, Chen SD Mathematic models help interpret experimental results and accelerate tissue engineering developments. We develop in this paper a hybrid cellular automata model that combines the differential nutrient transport equation to investigate the nutrient limited cell construct development for cartilage tissue engineering. Individual cell behaviors of migration, contact inhibition and cell collision, coupled with the cell proliferation regulated by oxygen concentration were carefully studied. Simplified two-dimensional simulations were performed. Using this model, we investigated the influence of cell migration speed on the overall cell growth within in vitro cell scaffolds. It was found that intense cell motility can enhance initial cell growth rates. However, since cell growth is also significantly modulated by the nutrient contents, intense cell motility with conventional uniform cell seeding method may lead to declined cell growth in the final time because concentrated cell population has been growing around the scaffold periphery to block the nutrient transport from outside culture media. Therefore, homogeneous cell seeding may not be a good way of gaining large and uniform cell densities for the final results. We then compared cell growth in scaffolds with various seeding modes, and proposed a seeding mode with cells initially residing in the middle area of the scaffold that may efficiently reduce the nutrient blockage and result in a better cell amount and uniform cell distribution for tissue engineering construct developments. PMID: 19808041 [PubMed - as supplied by publisher] |
| Cartilage outgrowth in fibrin scaffolds.
October 8, 2009 at 7:17 am
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| | Cartilage outgrowth in fibrin scaffolds. Am J Rhinol Allergy. 2009 Sep-Oct;23(5):486-91 Authors: Sage A, Chang AA, Schumacher BL, Sah RL, Watson D BACKGROUND: Fibrin glue has been a favorable hydrogel in cartilage tissue engineering, but implantation of chondrocyte-fibrin suspensions have resulted in volume loss. In this study, human septal cartilage chips were seeded onto a fibrin scaffold, and cellular proliferation and production of cartilaginous extracellular matrix (ECM) were evaluated. METHODS: Human septal cartilage was diced into cartilage chips and encased with and without fibrin glue. Four conditions were initially tested for DNA content and glycosaminoglycan (GAG) production: (1) control medium in tissue culture, (2) control medium with fibrin glue, (3) collagenase-supplemented medium in tissue culture, and (4) collagenase-supplemented medium seeded in fibrin glue. Cartilage chips cultured in collagenase-treated medium were then seeded onto either cell culture plates, suspended in alginate, or mixed with fibrin. Cellular proliferation, GAG production, and histochemistry were evaluated. RESULTS: Fibrin preparations increased cellular proliferation and DNA content. GAG levels were highest in collagenase-treated samples encased in fibrin. Cartilage chips treated with collagenase showed increased cellular proliferation in the fibrin preparations compared with preparations without fibrin. GAG increased with the addition of fibrin when compared with explant. Histochemistry revealed increased GAG accumulation in the regions between the cartilage chips with the addition of fibrin. CONCLUSION: Adding fibrin glue to collagenase-treated cartilage chips results in increased proliferation and maintains ECM production and, therefore, may facilitate generation of cartilaginous tissue for use in reconstructive surgery. PMID: 19807980 [PubMed - in process] |
| The Effects of ERK1/2 Inhibitor on the Chondrogenesis From Bone Marrow- and Adipose Tissue-derived Multipotent Mesenchymal Stromal Cells.
October 8, 2009 at 7:17 am
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| | The Effects of ERK1/2 Inhibitor on the Chondrogenesis From Bone Marrow- and Adipose Tissue-derived Multipotent Mesenchymal Stromal Cells. Tissue Eng Part A. 2009 Oct 6; Authors: Kim HJ, Im GI This study tested the hypothesis that mitogen-activated protein kinase (MAPK) inhibitors suppress hypertrophy and enhance chondrogenesis during chondrogenesis from multipotent mesenchymal stromal cells. The effects of PD98059 (an ERK1/2 inhibitor) and SB203580 (a p38 inhibitor) were tested on bone marrow- (BMMSCs) and adipose tissue-derived MSCs (ATMSCs). In-vitro pellet cultures were carried out using 2.5 x 10<sup>5</sup> MSCs in chondrogenic medium containing 5 ng/ml of TGF-beta2 for BMMSCs, and 5 ng/ml of TGF-beta2 and 100 ng/ml of BMP-7 for ATMSCs. From the 14th day of culture, the pellets were additionally treated with PD98059 or SB203580. After 14 more days of in-vitro culture, pellets were harvested for analysis. PD98059 increased DNA contents and GAG amounts in BMMSCs and ATMSCs, whereas SB203580 had little effect. COL1A1 mRNA decreased to almost a quarter in BMMSCs treated with PD98059. The mRNA levels of COL2A1 and SOX-9 increased several-fold in both cells after PD98059 treatment, whereas SB203580 had only a slight effect. The gene expression of COL10A1 and Runx-2 decreased by a half after PD98059 treatment in BMMSCs, and decreased by less in ATMSCs. SB203580 elevated COL10A1 and Runx-2 gene expressions in both cell types. Safranin-O staining and immunohistochemistry generally mirrored findings from real-time PCR except for diminished expression of type I collagen in ATMSCS, and more pronounced decrease in type X collagen and Runx-2 after PD98059 treatment in BMMSCs. Our study demonstrated that PD98059 suppressed hypertrophy and promoted chondrogenesis from MSCs, and provides a ground for using them in cartilage tissue engineering. PMID: 19807253 [PubMed - as supplied by publisher] |
| Synthesis and Characterization of Hydroxyl-Functionalized Caprolactone Copolymers and Their Effect on Adhesion, Proliferation, and Differentiation of Human Mesenchymal Stem Cells.
October 8, 2009 at 7:17 am
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| | Synthesis and Characterization of Hydroxyl-Functionalized Caprolactone Copolymers and Their Effect on Adhesion, Proliferation, and Differentiation of Human Mesenchymal Stem Cells. Biomacromolecules. 2009 Oct 6; Authors: Seyednejad H, Vermonden T, Fedorovich NE, van Eijk R, van Steenbergen MJ, Dhert WJ, van Nostrum CF, Hennink WE The aim of this study was to develop new hydrophilic polyesters for tissue engineering applications. In our approach, poly(benzyloxymethyl glycolide-co-epsilon-caprolactone)s (pBHMG-CLs) were synthesized through melt copolymerization of epsilon-caprolactone (CL) and benzyl-protected hydroxymethyl glycolide (BHMG). Deprotection of the polymers yielded copolymers with pendant hydroxyl groups, poly(hydroxymethylglycolide-co-epsilon-caprolactone) (pHMG-CL). The synthesized polymers were characterized by GPC, NMR, and DSC techniques. The resulting copolymers consisting of up to 10% of HMG monomer were semicrystalline with a melting temperature above body temperature. Water contact angle measurements of polymeric films showed that increasing HMG content resulted in higher surface hydrophilicity, as evidenced from a decrease in receding contact angle from 68 degrees for PCL to 40 degrees for 10% HMG-CL. Human mesenchymal stem cells showed good adherence onto pHMG-CL films as compared to the more hydrophobic PCL surfaces. The cells survived and were able to differentiate toward osteogenic lineage on pHMG-CL surfaces. This study shows that the aforementioned hydrophilic polymers are attractive candidates for the design of scaffolds for tissue engineering applications. PMID: 19807059 [PubMed - as supplied by publisher] |
| In vivo model for evaluating the effects of mechanical stimulation on tissue-engineered bone repair.
October 8, 2009 at 7:17 am
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| | In vivo model for evaluating the effects of mechanical stimulation on tissue-engineered bone repair. J Biomech Eng. 2009 Aug;131(8):084502 Authors: Boerckel JD, Dupont KM, Kolambkar YM, Lin AS, Guldberg RE It has long been known that the bone adapts according to the local mechanical environment. To date, however, a model for studying the effects of functional mechanical loading on tissue-engineered bone repair in vivo has not yet been established. We have developed a rat femoral defect model, in which ambulatory loads are transduced through the implanted tissue-engineered construct to elucidate the role of the mechanical environment in functional restoration of a large bone defect. This model uses compliant fixation plates with integrated elastomeric segments, which allow transduction of ambulatory loads. Multiaxially and uniaxially compliant plates were characterized by mechanical testing and evaluated using in vivo pilot studies. In the first study, experimental limbs were implanted with multiaxial plates, which have a low stiffness in multiple loading modes. In the second study, experimental limbs were stabilized by a uniaxial plate, which allowed only axial deformation of the defect. X-ray scans and mechanical testing revealed that the multiaxial plates were insufficient to stabilize the defect and prevent fracture under ambulatory loads as a result of low flexural and torsional stiffness. The uniaxial plates, however, maintained integrity of the defect when implanted over a 12 week period. Postmortem microCT scans revealed a 19% increase in bone volume in the axially loaded limb compared with the contralateral standard control, and postmortem mechanical testing indicated that torsional strength and stiffness were increased 25.6- and 3.9-fold, respectively, compared with the control. Finite element modeling revealed high strain gradients in the soft tissue adjacent to the newly formed bone within the implanted construct. This study introduces an in vivo model for studying the effects of physiological mechanical loading on tissue-engineered bone repair. Preliminary results using this new in vivo model with the uniaxially compliant plate showed positive effects of load-bearing on functional defect repair. PMID: 19604025 [PubMed - indexed for MEDLINE] |
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