|  |  |  | | | | | pubmed: adipose stem cell | | | | | | | | | | | | | | | | | | | Characterisation of the human nucleus pulposus cell phenotype and evaluation of novel marker gene expression to define adult stem cell differentiation. Arthritis Rheum. 2010 Aug 18; Authors: Minogue BM, Richardson SM, Zeef LA, Freemont AJ, Hoyland JA OBJECTIVE.: Development of stem cell therapies for regeneration of the nucleus pulposus (NP) are hindered by the lack of specific markers to distinguish NP cells from articular chondrocytes (AC cells). This study details, for the first time, gene expression profiling to identify the human NP phenotype and assesses whether the identified markers can distinguish mesenchymal stem cell (MSC) differentiation to a correct NP cell phenotype. METHODS.: Affymetrix Microarrays were conducted on human NP and AC cells and differential expression levels for several positive (NP) and negative (AC) marker genes validated by qRT-PCR. Novel marker gene and protein expression was also assessed in human bone marrow-derived MSCs (BM-MSCs) and adipose-derived MSCs (ASCs) following differentiation in type I collagen gels. RESULTS.: Analysis identified 12 NP positive and 36 negative marker genes differentially expressed >/=20 fold and for a subset (NP positive genes PAX1, FOXF1, HBB, CA12 and OVOS2; AC genes GDF10, CYTL1, IBSP and FBLN1) differential expression was confirmed by qRT-PCR. Differentiated BM-MSCs and ASCs demonstrated significant increases in the novel NP markers PAX1 and FOXF1. ASCs lacked expression of the AC markers IBSP and FBLN1, whereas BM-MSCs lacked expression of the AC marker IBSP but expressed FBLN1. CONCLUSION.: This study has identified the phenotypic profile of human NP cells. Importantly these markers can be used to determine the in vitro differentiation of MSCs to an NP-like rather than an AC-like phenotype. Interestingly, these results suggest that ASCs may be a more appropriate cell type than BM-MSCs for IVD tissue engineering. PMID: 20722018 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The effect of the local delivery of alendronate on human adipose-derived stem cell-based bone regeneration. Biomaterials. 2010 Aug 16; Authors: Wang CZ, Chen SM, Chen CH, Wang CK, Wang GJ, Chang JK, Ho ML Recent studies have shown that alendronate (Aln) enhances the osteogenesis of osteoblasts and bone marrow mesenchymal stem cells. In this study, we hypothesize that Aln may act as an osteo-inductive factor to stimulate the osteogenic differentiation of human adipose-derived stem cells (hADSCs) for bone regeneration. The in vitro effect of Aln (1-10 muM) on the osteogenic ability of hADSCs was evaluated by examining mineralization and alkaline phosphatase (ALP) activity. Bone morphogenetic protein 2 (BMP2) expression was measured using a real-time polymerase chain reaction and western blot analysis. Our results indicated that 5 muM Aln was sufficient to enhance BMP2 expression, ALP activity and mineralization in hADSCs. The in vivo effect of locally administered Aln on bone repair was examined in a rat critical-sized (7-mm) calvarial defect that was implanted with a hADSC-seeded poly(lactic-co-glycolic acid) (PLGA) scaffold. Aln (5 muM/100 mul/day) was injected locally into the defect site for one week. New bone formation was evaluated by radiographic and histological analyses at 8 and 12 weeks post-implantation. The expression levels of human BMP2 (hBMP2) and hADSC localization in defect sites were examined using immunohistochemistry analysis and fluorescent in situ hybridization, respectively. Results showed that local treatment of Aln on hADSC-seeded PLGA scaffolds at week 12 had a maximal effect on bone regeneration, enhancing mineralization and bone matrix formation. In addition, hADSCs and hBMP2 were also detected at the defect sites. These results demonstrated that local delivery of Aln, a potent osteo-inductive factor, enhances hADSC osteogenesis and bone regeneration. PMID: 20719378 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Locally Administered Adipose-derived Stem Cells Accelerate Wound Healing through Differentiation and Vasculogenesis. Cell Transplant. 2010 Aug 18; Authors: Nie C, Yang D, Xu J, Si Z, Jin X, Zhang J Despite advances in wound closure techniques and devices, there is still a critical need for new methods of enhancing the healing process to achieve optimal outcomes. Recently, stem cell therapy has emerged as a new approach to accelerate wound healing. Adipose-derived stem cells (ASCs) hold great promise for wound healing, which are multipotential stem cells capable of differentiation into various cell lineages and secretion of angiogenic growth factors. The aim of this study was to evaluate the benefit of ASCs on wound healing and then investigate the probable mechanisms. ASCs characterized by flow cytometry were successfully isolated and cultured. An excisional wound healing model in rat was used to determine the effects of locally administered ASCs. The gross and histological results showed that ASCs significantly accelerated wound closure in normal and diabetic rat, including increased epithelialization and granulation tissue deposition. Furthermore, we applied GFP-labeled ASCs on wounds to determine whether ASCs could differentiate along multiple lineages of tissue regeneration in the specific microenvironment. Immunofluorescent analysis indicated that GFP-expressing ASCs were co-stained with pan-cytokeratin and CD31 respectively, indicating spontaneous site-specific differentiation into epithelial and endothelial lineages. These data suggest that ASCs not only contribute to cutaneous regeneration, but also participate in new vessels formation. Moreover, ASCs were found to secret angiogenic cytokines in vitro and in vivo, including VEGF, HGF and FGF2, which increase neovascularization and enhance wound healing in injured tissues. In conclusion, our results demonstrate that ASCs therapy could accelerate wound healing through differentiation and vasculogenesis and might represent a novel therapeutic approach in cutaneous wounds. PMID: 20719083 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The regulatory role of c-MYC on HDAC2 and PcG expression in human multipotent stem cells. J Cell Mol Med. 2010 Aug 16; Authors: Bhandari DR, Seo KW, Jung JW, Kim HS, Yang SR, Kang SK, Kang KS Abstract c-MYC is a well known nuclear oncoprotein having multiple functions in cell proliferation, apoptosis and cellular transformation. Chromosomal modification is also important to the differentiation and growth of stem cells. Histone Deacethylase (HDAC) and Polycomb group (PcG) family genes are well known chromosomal modification genes. The aim of this study was to elucidate the role of c-MYC in the expression of chromosomal modification via the HDAC family genes in human mesenchymal stem cells (hMSCs). To achieve this goal, c-MYC expression was modified by gene knock-down and over-expression via lentivirus vector. Using the modified c-MYC expression, our study was focused on cell proliferation, differentiation and cell cycle. Furthermore, the relationship of c-MYC with HDAC2 and PcG genes was also examined. The cell proliferation and differentiation were checked and shown to be dramatically decreased in c-MYC knocked-down human umbilical cord blood-derived MSCs (hUCB-MSCs), whereas they were increased in c-MYC over-expressing cells. Similarly, RT-PCR and Western Blotting results revealed that HDAC2 expression was decreased in c-MYC knocked-down and increased in c-MYC over-expressing hMSCs. Database indicates presence of c-MYC binding motif (CACGTG) in HDAC2 promoter region, which was confirmed by Chromatin immunoprecipitation (ChIP) assay. The influence of c-MYC and HDAC2 on PcG expression was confirmed. This might indicate the regulatory role of c-MYC over HDAC2 and PcG genes. c-MYCs' regulatory role over HDAC2 was also confirmed in human adipose tissue-derived MSCs (hAD-MSCs) and bone-marrow derived MSCs (hBM-MSCs). From this finding, it can be concluded that c-MYC plays a vital role in cell Proliferation & differentiation via chromosomal modification. PMID: 20716118 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Human progenitor cells derived from cardiac adipose tissue ameliorate myocardial infarction in rodents. J Mol Cell Cardiol. 2010 Aug 13; Authors: Bayes-Genis A, Soler-Botija C, Farré J, Sepúlveda P, Raya A, Roura S, Prat-Vidal C, Gálvez-Montón C, Montero JA, Büscher D, Belmonte JC Myocardial infarction caused by vascular occlusion results in the formation of nonfunctional fibrous tissue. Cumulative evidence indicates that cell therapy modestly improves cardiac function; thus, novel cell sources with the potential to repair injured tissue are actively sought. Here, we identify and characterize a cell population of cardiac adipose tissue-derived progenitor cells (ATDPCs) from biopsies of human adult cardiac adipose tissue. Cardiac ATDPCs express a mesenchymal stem cell-like marker profile (strongly positive for CD105, CD44, CD166, CD29 and CD90) and have immunosuppressive capacity. Moreover, cardiac ATDPCs have an inherent cardiac-like phenotype and were able to express de novo myocardial and endothelial markers in vitro, but not to differentiate into adipocytes. In addition, when cardiac ATDPCs were transplanted into injured myocardium in mouse and rat models of myocardial infarction, the engrafted cells expressed cardiac (troponin I, sarcomeric alpha-actinin) and endothelial (CD31) markers, vascularization increased and infarct size was reduced in mice and rats. Moreover, significant differences between control and cell-treated groups were found in fractional shortening and ejection fraction, and the anterior wall remained significantly thicker 30days after cardiac delivery of ATDPCs. Finally, cardiac ATDPCs secreted proangiogenic factors under in vitro hypoxic conditions, suggesting a paracrine effect to promote local vascularization. Our results indicate that the population of progenitor cells isolated from human cardiac adipose tissue (cardiac ATDPCs) may be valid candidates for future use in cell therapy to regenerate injured myocardium. PMID: 20713059 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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