Current Issue : July - September Volume : 2017 Issue Number : 3 Articles : 5 Articles
The use of human pluripotent stem cells in basic and translational cardiac research requires efficient differentiation protocols\ntowards cardiomyocytes. In vitro differentiation yields heterogeneous populations of ventricular-, atrial-, and nodal-like cells\nhindering their potential applications in regenerative therapies.We described the effect of the growth factor Activin A during early\nhuman embryonic stem cell fate determination in cardiac differentiation.Addition of high levels ofActivinAduring embryoid body\ncardiac differentiation augmented the generation of endoderm derivatives, which in turn promoted cardiomyocyte differentiation.\nMoreover, a dose-dependent increase in the coreceptor expression of the TGF-...
Background: The native articular cartilage lacks the ability to heal. Currently, ex vivo expanded chondrocytes or\nbone marrow-derived mesenchymal stem cells are used to regenerate the damaged cartilage. With unlimited\nself-renewal ability and multipotency, human induced pluripotent stem cells (hiPSCs) have been highlighted as a\nnew replacement cell source for cartilage repair. Still, further research is needed on cartilage regeneration using\ncord blood mononuclear cell-derived hiPSCs (CBMC-hiPSCs).\nMethods: Human iPSCs were generated from CBMCs using the Sendai virus. The characterization of CBMC-hiPSCs\nwas performed by various assays. Embryonic bodies (EBs) were obtained using CBMC-hiPSCs, and outgrowth cells\nwere induced by plating the EBs onto a gelatin-coated plate. Expanded outgrowth cells were detached and\ndissociated for chondrogenic differentiation. Outgrowth cells were differentiated into chondrogenic lineage with\npellet culture. Chondrogenic pellets were maintained for 30 days. The quality of chondrogenic pellets was\nevaluated using various staining and genetic analysis of cartilage-specific markers.\nResults: Reprogramming was successfully done using CBMCs. CBMC-hiPSCs (n = 3) showed high pluripotency and\nnormal karyotype. Chondrogenic pellets were generated from the outgrowth cells derived from CBMC-hiPSC EBs.\nThe generated chondrogenic pellets showed high expression of chondrogenic genetic markers such as ACAN,\nCOMP, COL2A1, and SOX9. The production of extracellular matrix (ECM) proteins was confirmed by safranin O,\nalcian blue and toluidine blue staining. Expression of collagen type II and aggrecan was detected in the\naccumulated ECM by immunohistological staining. Chondrogenic pellets showed low expression of fibrotic and\nhypertrophic cartilage marker, collagen type I and X.\nConclusions: This study reveals the potential of CBMC-hiPSCs as a promising candidate for cartilage regeneration...
Mesenchymal stem cells (MSCs) are involved in anti-inflammatory events and tissue repair; these functions are activated by\ntheir migration or homing to inflammatory tissues in response to various chemokines. However, the mechanism by which MSCs\ninteract with other cell types in inflammatory tissue remains unclear. We investigated the role of periodontal ligament fibroblasts\n(PDL-Fs) in regulating the anti-inflammatory and osteogenic abilities of bone marrow-derived- (BM-) MSCs. The expression\nof monocyte chemotactic protein- (MCP-)1 was significantly enhanced by stimulation of PDL-Fs with inflammatory cytokines.\nMCP-1 induced the migratory ability of BM-MSCs but not PDL-Fs. Expression levels of anti-inflammatory and inflammatory\ncytokines were increased and decreased, respectively, by direct-contact coculture between MSCs and PDL-Fs. In addition, the\ndirect-contact coculture enhanced the expression of MSC markers that play important roles in the self-renewal and maintenance\nof multipotency of MSCs, which in turn induced the osteogenic ability of the cells. These results suggest that MCP-1 induces the\nmigration and homing of BM-MSCs into the PDL inflammatory tissue. The subsequent adherence of MSCs to PDL-Fs plays an\nimmunomodulatory role to terminate inflammation during wound healing and upregulates the expression stem cell markers to\nenhance the stemness of MSCs, thereby facilitating bone formation in damaged PDL tissue....
Objectives. Acute lung injury (ALI) is a common clinical critical disease. Stem cells transplantation is recognized as an effective\nway to repair injured lung tissues. The present study was designed to evaluate the effects of mesenchymal stem cells (MSCs) on\nrepair of lung and its mechanism. Methods. MSCs carrying GFP were administrated via trachea into wild-type SD rats 4 hours\nlater after LPS administration.The lung histological pathology and the distribution of MSCs were determined by HE staining and\nfluorescence microscopy, respectively. Next, differentially expressed HOX genes were screened by using real-time PCR array and\nabnormal expression and function of Hox A9 were analyzed in the lung and the cells. Results. MSCs promoted survival rate of ALI\nanimals. The expression levels ofmultipleHOX genes had obvious changes after MSCs administration and HOX A9 gene increased\nby 5.94-fold after MSCs administration into ALI animals. HOX A9 was distributed in endothelial cells and epithelial cells in animal\nmodels and overexpression of Hox A9 can promote proliferation and inhibit inflammatory adhesion of MSCs. Conclusion. HoxA9\noverexpression induced by MSCs may be closely linked with lung repair after endotoxin shock....
Background: Generation of large quantities of endothelial cells is highly desirable for vascular research, for the\ntreatment of ischemia diseases, and for tissue regeneration. To achieve this goal, we developed a simple, chemically\ndefined culture system to efficiently and rapidly differentiate endothelial cells from human pluripotent stem cells by\ngoing through an MESP1 mesoderm progenitor stage.\nMethods: Mesp1 is a key transcription factor that regulates the development of early cardiovascular tissue. Using\nan MESP1-mTomato knock-in reporter human embryonic stem cell line, we compared the gene expression profiles\nof MESP1+ and MESP1âË?â?? cells and identified new signaling pathways that may promote endothelial differentiation.\nWe also used a 3D scaffold to mimic the in vivo microenvironment to further improve the efficiency of endothelial\ncell generation. Finally, we performed cell transplantation into a critical limb ischemia mouse model to test the\nrepairing potential of endothelial-primed MESP1+ cells.\nResults: MESP1+ mesoderm progenitors, but not MESP1âË?â?? cells, have strong endothelial differentiation potential. Global\ngene expression analysis revealed that transcription factors essential for early endothelial differentiation were enriched\nin MESP1+ cells. Interestingly, MESP1 cells highly expressed Sphingosine-1-phosphate (S1P) receptor and the addition\nof S1P significantly increased the endothelial differentiation efficiency. Upon seeding in a novel 3D microniche\nand priming with VEGF and bFGF, MESP1+ cells markedly upregulated genes related to vessel development and\nregeneration. 3D microniches also enabled long-term endothelial differentiation and proliferation from MESP1+\ncells with minimal medium supplements. Finally, we showed that transplanting a small number of endothelial-primed\nMESP1+ cells in 3D microniches was sufficient to mediate rapid repair of a mouse model of critical limb ischemia.\nConclusions: Our study demonstrates that combining MESP1+ mesoderm progenitor cells with tissue-engineered\n3D microniche and a chemically defined endothelial induction medium is a promising route to maximizing the\nproduction of endothelial cells in vitro and augment their regenerative power in vivo....
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