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| Reprogramming with defined factors: from induced pluripotency to induced transdifferentiation.
July 10, 2010 at 8:37 AM
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| | Reprogramming with defined factors: from induced pluripotency to induced transdifferentiation. Mol Hum Reprod. 2010 Jul 8; Authors: Masip M, Veiga A, Izpisúa JC, Simón C Ever since work on pluripotency induction was originally published, reporting the reprogramming of somatic cells to induced pluripotent stem cells, (iPS cells) by the ectopic expression of the four transcription factors Oct4, Sox2, Klf4 and c-Myc, high expectations regarding their potential use for regenerative medicine have emerged. Very recently, the direct conversion of fibroblasts into functional neurons with no prior pluripotent stage has been described. Interconversion between adult cells from ontogenically different lineages by an induced transdifferentiation process based on the overexpression of a cocktail of transcription factors, while avoiding transition through an embryonic stem cell-like state, provides a new impetus in the field of regenerative medicine. Here we review the induced reprogramming of somatic cells with defined factors and analyze their potential clinical use. Beginning with induced pluripotency, we summarize the initial objections including their extremely low efficiency and the risk of tumor generation. We also review recent reports describing iPS cells' capacity to generate viable offspring through tetraploid complementation, the most restrictive pluripotency criterion. Finally, we explore the available evidence for "induced transdifferentiated (iT) cells," as a novel tool for adult cell fate modification. PMID: 20616150 [PubMed - as supplied by publisher] | | |
| MicroRNA miR-125a controls hematopoietic stem cell number.
July 10, 2010 at 8:37 AM
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| | MicroRNA miR-125a controls hematopoietic stem cell number. Proc Natl Acad Sci U S A. 2010 Jul 8; Authors: Guo S, Lu J, Schlanger R, Zhang H, Wang JY, Fox MC, Purton LE, Fleming HH, Cobb B, Merkenschlager M, Golub TR, Scadden DT MicroRNAs influence hematopoietic differentiation, but little is known about their effects on the stem cell state. Here, we report that the microRNA processing enzyme Dicer is essential for stem cell persistence in vivo and a specific microRNA, miR-125a, controls the size of the stem cell population by regulating hematopoietic stem/progenitor cell (HSPC) apoptosis. Conditional deletion of Dicer revealed an absolute dependence for the multipotent HSPC population in a cell-autonomous manner, with increased HSPC apoptosis in mutant animals. An evolutionarily conserved microRNA cluster containing miR-99b, let-7e, and miR-125a was preferentially expressed in long-term hematopoietic stem cells. MicroRNA miR-125a alone was capable of increasing the number of hematopoietic stem cells in vivo by more than 8-fold. This result was accomplished through a differentiation stage-specific reduction of apoptosis in immature hematopoietic progenitors, possibly through targeting multiple proapoptotic genes. Bak1 was directly down-regulated by miR-125a and expression of a 3'UTR-less Bak1 blocked miR-125a-induced hematopoietic expansion in vivo. These data demonstrate cell-state-specific regulation by microRNA and identify a unique microRNA functioning to regulate the stem cell pool size. PMID: 20616003 [PubMed - as supplied by publisher] | | |
| Combinatorial Extracellular Matrices for Human Embryonic Stem Cell Differentiation in 3D.
July 10, 2010 at 8:37 AM
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| | Combinatorial Extracellular Matrices for Human Embryonic Stem Cell Differentiation in 3D. Biomacromolecules. 2010 Jul 9; Authors: Yang F, Cho SW, Son SM, Hudson SP, Bogatyrev S, Keung L, Kohane DS, Langer R, Anderson DG Embryonic stem cells (ESCs) are promising cell sources for tissue engineering and regenerative medicine. Scaffolds for ESC-based tissue regeneration should provide not only structural support, but also signals capable of supporting appropriate cell differentiation and tissue development. Extracellular matrix (ECM) is a key component of the stem cell niche in vivo and can influence stem cell fate via mediating cell attachment and migration, presenting chemical and physical cues, as well as binding soluble factors. Here we investigated the effects of combinatorial extracellular matrix proteins on controlled human ESC (hESC) differentiation. Varying ECM compositions in 3D markedly affects cell behavior, and optimal compositions of ECM hydrogels are identified that facilitate specific-lineage differentiation of stem cells. To our knowledge, this is the first combinatorial analysis of ECM hydrogels for their effects on hESC differentiation in 3D. The 3D matrices described herein may provide a useful platform for studying the interactive ECM signaling in influencing stem cell differentiation. PMID: 20614932 [PubMed - as supplied by publisher] | | |
| Proliferation of myoblast skeletal cells on three-dimensional supermacroporous cryogels.
July 10, 2010 at 8:28 AM
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| | Proliferation of myoblast skeletal cells on three-dimensional supermacroporous cryogels. Int J Biol Sci. 2010;6(4):371-81 Authors: Singh D, Nayak V, Kumar A Cardiac and skeletal muscle tissue engineering provides a smart approach to overcome problems associated with organ transplantation and cardiac tissue and also lays a platform for superior alternative approaches in muscle regeneration. The aim of the study was to demonstrate cryogel scaffold potential in the field of skeletal muscle and cardiac tissue engineering. Poly-hydroxyethyl methacrylate (pHEMA)-gelatin cryogel scaffold was synthesized using cryogelation technique and such a designed material is being reported first time. Rheology study of the pHEMA-gelatin (HG) suggested that the cryogel scaffolds were stable at different temperatures and phase angle remained constant in both dry and wet state. HG cryogel was able to bear increased stress without leading to deformation. Monitoring the hydration of HG scaffold showed shift from a stiff to a more pliable material and upon continuing hydration, shear modulus remained constant with no further change observed. However, the change in phase angle <0.24 masculine indicates a gradual increase in stiffness of the material over time. Scaffold synthesised using such polymer combinations gave cells a native environment for proliferation and surface stiffness have shown to help in differentiation of the cells. Myoskeletal cell lines were cultured on these scaffolds to check the biocompatibility and cell proliferation. Alamar blue assay performed over a period of 3 weeks analysed the metabolic activity of cells which showed more than 60% increase in the total cellular activity. DNA content of cells was found to be directly related to number of cells present at a given time point and this was found to have increased by more than 50% in 3 weeks. Since in 3-D scaffold the surface area is more in comparison to 2-D, hence better cell proliferation is observed. Hoechst and DAPI staining showed tubular structure and alignment of the cells during formation of the tubules shows promising cellular response to the cryogel matrix. The mechanical strength, stiffness and elastic measurements of the scaffold indicated potential application of these materials for skeletal and cardiac tissue engineering. PMID: 20617130 [PubMed - in process] | | |
| The effect of incorporation of exogenous stromal cell-derived factor-1 alpha within a knitted silk-collagen sponge scaffold on tendon regeneration.
July 10, 2010 at 8:28 AM
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| | The effect of incorporation of exogenous stromal cell-derived factor-1 alpha within a knitted silk-collagen sponge scaffold on tendon regeneration. Biomaterials. 2010 Jul 6; Authors: Shen W, Chen X, Chen J, Yin Z, Heng BC, Chen W, Ouyang HW This study developed a bioactive knitted silk-collagen sponge scaffold by incorporation of exogenous SDF-1 alpha, to enable selective migration and homing of cells for in situ tendon regeneration. With in vitro studies, it was observed that CXCR4 gene expression and migration of bone mesenchymal stromal cells and hypo-dermal fibroblasts were more sensitive to exogenous SDF-1 alpha, while expression of tendon repair gene markers by hypo-dermal fibroblasts and Achilles tendon fibroblasts were more sensitive to exogenous SDF-1 alpha. With a rat Achilles tendon injury model, exogenous SDF-1 alpha was shown to reduce infiltration of inflammatory cells and enhance migration of fibroblast-like cells into the scaffold at 4 days and 1 week post-surgery. After 4 weeks, SDF-1 alpha treated tendon had increased expression of tendon repair gene markers and endogenous SDF-1 alpha, exhibited more physiological microstructures with larger diameter collagen fibrils, and had better biomechanical properties than the control group. Hence, our bioactive scaffold improved efficacy of tendon regeneration by increasing the recruitment of fibroblast-like cells, enhancing local endogenous SDF-1 alpha and tendon extracellular matrix production, and decreasing accumulation of inflammatory cells. Incorporation of SDF-1 alpha within a knitted silk-collagen sponge scaffold can therefore be a practical application for tendon tissue engineering. PMID: 20615544 [PubMed - as supplied by publisher] | | |
| Preliminary Investigation of Airgap Electrospun Silk-Fibroin-Based Structures for Ligament Analogue Engineering.
July 10, 2010 at 8:28 AM
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| | Preliminary Investigation of Airgap Electrospun Silk-Fibroin-Based Structures for Ligament Analogue Engineering. J Biomater Sci Polym Ed. 2010 Jul 2; Authors: Sell SA, McClure MJ, Ayres CE, Simpson DG, Bowlin GL The process of electrospinning has proven to be highly beneficial for use in a number of tissue-engineering applications due to its ease of use, flexibility and tailorable properties. There have been many publications on the creation of aligned fibrous structures created through various forms of electrospinning, most involving the use of a metal target rotating at high speeds. This work focuses on the use of a variation known as airgap electrospinning, which does not use a metal collecting target but rather a pair of grounded electrodes equidistant from the charged polymer solution to create highly aligned 3D structures. This study involved a preliminary investigation and comparison of traditionally and airgap electrospun silk-fibroin-based ligament constructs. Structures were characterized with SEM and alignment FFT, and underwent porosity, permeability, and mechanical anisotropy evaluation. Preliminary cell culture with human dermal fibroblasts was performed to determine the degree of cellular orientation and penetration. Results showed airgap electrospun structures to be anisotropic with significantly increased porosity and cellular penetration compared to their traditionally electrospun counterparts. PMID: 20615358 [PubMed - as supplied by publisher] | | |
| Novel Scaffolds Based on Poly(2-hydroxyethyl methacrylate) Superporous Hydrogels for Bone Tissue Engineering.
July 10, 2010 at 8:28 AM
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| | Novel Scaffolds Based on Poly(2-hydroxyethyl methacrylate) Superporous Hydrogels for Bone Tissue Engineering. J Biomater Sci Polym Ed. 2010 Jul 2; Authors: Cetin D, Kahraman AS, Gümüşderelioğlu M In this study, poly(2-hydroxyethyl methacrylate) (pHEMA)-based superporous hydrogels were synthesized by radical polymerization of 2-hydroxyethyl methacrylate (HEMA) in the presence of a gas blowing agent, sodium bicarbonate. These hydrogels are: pHEMA, pHEMA-gelatin, glycerol phosphate (GP) cross-linked pHEMA-gelatin, glutaraldehyde (GA) cross-linked pHEMA-gelatin superporous hydrogels (SPHs) and pHEMA-hydroxyapatite (HA) superporous hydrogel composites (SPHCs). The hydrogels have a structure of interconnected pores with pore sizes of approx. 500 mum. Although the extent of swelling decreased when gelatin and HA were incorporated to the pHEMA structure, the time to reach the equilibrium swelling (approx. 20 s) was not affected so much. In the presence of gelatin and cross-linkers, mechanical properties significantly improved when compared with pHEMA SPH. Among all the synthesized hydrogels, pHEMA-HA SPHC showed great improvement in mechanical strength and its elastic modulus value was 0.027+/-0.002 N/mm(2). Osteogenic activities of pHEMA-based scaffolds were examined by preosteoblastic MC3T3-E1 cell-culture studies. The mitochondrial activity test (MTT) showed that gelatin-containing scaffolds stimulated cell proliferation compared with other scaffolds, while alkaline phosphatase levels (ALP) and mineralization were found highest for the GP cross-linked pHEMA-gelatin SPH. However, pHEMA SPH and pHEMA-HA SPHC did not support cell proliferation and also differentiation. In conclusion, pHEMA-gelatin SPH and GP cross-linked pHEMA-gelatin SPH can be considered as potential scaffolds for bone tissue-engineering applications. PMID: 20615330 [PubMed - as supplied by publisher] | | |
| Cross-Linking of Gelatin and Chitosan Complex Nanofibers for Tissue-Engineering Scaffolds.
July 10, 2010 at 8:28 AM
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| | Cross-Linking of Gelatin and Chitosan Complex Nanofibers for Tissue-Engineering Scaffolds. J Biomater Sci Polym Ed. 2010 Jul 2; Authors: Qian YF, Zhang KH, Chen F, Ke QF, Mo XM The aim of this study is to investigate cross-linked gelatin-chitosan nanofibers produced by means of electrospinning. Gelatin and chitosan nanofibers were electrospun and then cross-linked by glutaraldehyde (GTA) vapor at room temperature. Scanning electron microscopy (SEM) images showed that the cross-linked mats could keep their nanofibrous structure after being soaked in deionized water at 37 degrees C. The cross-linking mechanism was discussed based on FT-IR results. The two main mechanisms of cross-linking for chitosan and gelatin-chitosan complex are Schiff base reaction and acetalization reaction. For gelatin, the mechanism of cross-linking was Schiff base reaction. The mechanical properties of nanofibrous mats were improved after cross-linking. The biocompatibility of electrospun nanofibrous mats after cross-linking was investigated by the viability of porcine iliac endothelial cells (PIECs). The morphologies of PIECs on the cross-linked nanofibrous mats were observed by SEM. In addition, proliferation of PIECs was tested with the method of methylthiazol tetrazolium (MTT) assay. The results indicate that gelatin-chitosan nanofibrous mats could be a promising candidate for tissue-engineering scaffolds. PMID: 20615315 [PubMed - as supplied by publisher] | | |
| Electrospun Silk Fibroin-Hydroxybutyl Chitosan Nanofibrous Scaffolds to Biomimic Extracellular Matrix.
July 10, 2010 at 8:28 AM
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| | Electrospun Silk Fibroin-Hydroxybutyl Chitosan Nanofibrous Scaffolds to Biomimic Extracellular Matrix. J Biomater Sci Polym Ed. 2010 Jul 2; Authors: Zhang K, Qian Y, Wang H, Fan L, Huang C, Mo X Silk fibroin (SF)-hydroxybutyl chitosan (HBC) blend nanofibrous scaffolds were fabricated using 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) and trifluoroacetic acid (TFA) as solvents to biomimic the native ECM by electrospinning. SEM results showed that the average nanofibrous diameter increased when the content of HBC was raised from 20% to 100%. Whereas water contact angle measurements confirmed that SF/HBC nanofibrous scaffolds with different weight ratios were of good hydrophilicity. Both the tensile strength and the elongation at break were improved obviously when the weight ratio of SF to HBC was 20:80. (13)C-NMR clarified that SF and HBC molecules existed in H-bond interactions, but HBC did not induce SF conformation to transform from random coil form to beta-sheet structure. Moreover, the use of genipin vapour not only induced conformation of SF to convert from random coil to beta-sheet structure but also acted as a cross-linking agent for SF and HBC. Cell viability studies demonstrated that SF/HBC nanofibrous scaffolds presented good cellular compatibility. Thus, electrospun SF/HBC blended nanofibres may provide an ideal biomimic tissue-engineering scaffold. PMID: 20615313 [PubMed - as supplied by publisher] | | |
| Combinatorial Extracellular Matrices for Human Embryonic Stem Cell Differentiation in 3D.
July 10, 2010 at 8:28 AM
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| | Combinatorial Extracellular Matrices for Human Embryonic Stem Cell Differentiation in 3D. Biomacromolecules. 2010 Jul 9; Authors: Yang F, Cho SW, Son SM, Hudson SP, Bogatyrev S, Keung L, Kohane DS, Langer R, Anderson DG Embryonic stem cells (ESCs) are promising cell sources for tissue engineering and regenerative medicine. Scaffolds for ESC-based tissue regeneration should provide not only structural support, but also signals capable of supporting appropriate cell differentiation and tissue development. Extracellular matrix (ECM) is a key component of the stem cell niche in vivo and can influence stem cell fate via mediating cell attachment and migration, presenting chemical and physical cues, as well as binding soluble factors. Here we investigated the effects of combinatorial extracellular matrix proteins on controlled human ESC (hESC) differentiation. Varying ECM compositions in 3D markedly affects cell behavior, and optimal compositions of ECM hydrogels are identified that facilitate specific-lineage differentiation of stem cells. To our knowledge, this is the first combinatorial analysis of ECM hydrogels for their effects on hESC differentiation in 3D. The 3D matrices described herein may provide a useful platform for studying the interactive ECM signaling in influencing stem cell differentiation. PMID: 20614932 [PubMed - as supplied by publisher] | | | | 
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