In regenerative medicine, adult stem cells are the most encouraging cell types for cell-based therapies. as well as other challenges and obstacles will be highlighted. and gene expression was exhibited in a rabbit ear hypertrophic scar model by locally intralesional injection of ADSCs [31]. Cartilage and Intervertebral Disc Regeneration In the light of the aging population, the skeletal tissue is usually more and more affected. Consequently, today musculoskeletal disorders represent a major cause of disability and morbidity globally and result in enormous costs for health and social care systems. Chronic and inflammatory diseases of the joints MGC14452 and the spine, including osteoarthritis and low back pain caused by intervertebral disc degeneration, are major causes of disability in the seniors. In cell-based therapies for cartilage repair, transplanted ADSCs play a critical role in the efficacy of the therapy by interacting with local chondrocytes or cartilage explants in cartilage defects [32,33]. However, the involved mechanism in the paracrine influence of ADSCs on chondrocytes is usually still unclear. Studies show that the implantation of mixed ADSCs and chondrocytes into cartilage defects induces desirable in vivo healing outcomes. The BMP family members BMP-2, BMP-4, and BMP-5 are down-regulated, and VEGFB, HIF-1, FGF-2, and PDGF are significantly decreased after co-culture. These results suggest that crosstalk between ADSCs and chondrocytes might have potential in cartilage repair and regeneration and could be also beneficial for cartilage tissue engineering [34]. Cardiovascular and Myocardial Regeneration Molecular characterization of ADSCs not only has revealed their osteogenic, adipogenic and chondrogenic differentiation in vitro but also gives reason to suggest a myogenic potential of the ADSCs to further expand the mesodermal lineage. In recent years, cell therapies for cardiovascular and myocardial tissue regeneration have been an area of large interest. A variety of cell types have been shown to have a beneficial effect, especially for regeneration of the ischemic myocardium [35]. The paracrine factors can improve cardiac function by reducing the apoptosis of cardiomyocytes or by activating cardiac 901119-35-5 supplier stem cells to increase cardiomyogenesis [36]. The therapeutic potential of ADSCs in the setting of chronic heart failure or acute myocardial infarction has been investigated by injecting them intracoronary. The ADSCs engrafted in the infarct region 4 weeks after cell transplantation and improved cardiac function, perfusion, and remodeling after acute myocardial infarction [37,38]. In addition, ADSCs sparked the interest for application in cardiovascular tissue engineering and have been investigated as a source of interstitial cells to populate the heart valve constructs. It was shown that ADSCs can reproduce the major tissue structures that are required for proper valve functionality by producing matrix components, such as collagen and elastin, and by secreting matrix-enhancing or -degrading products [39,40]. Interestingly for the required anti-thrombogenicity of heart valve constructs, 901119-35-5 supplier ADSCs are capable of differentiating into cells with phenotypic and functional features of endothelial cells [39,40]. Ectodermal Potential of ADSCs Recently, it has been shown that ADSCs can express specific markers of both the neuronal (NSE, nestin, MAP2, -tubulin III) and the glial lineages (GFAP, NG2, p75 NGF receptor) when cultivated in the presence of the differentiation factors valproic acid, butylated hydroxyanisole, insulin, and hydrocortisone [41,42]. The observed neuronal differentiation potential of ADSCs could be beneficial in the cell-therapeutic 901119-35-5 supplier treatment of neuronal diseases, such as stroke [43] or Parkinson [44]. Stroke is usually a result of cerebral ischemia that triggers a cascade of both 901119-35-5 supplier physiological and biochemical events. Currently no medication is usually effective for the treatment of stroke. However, stem cell therapies have the potential to handle the effects of stroke [45]. More specifically, the ability of ADSCs to differentiate into neuron-like cells and other recent studies showing that human ADSCs significantly safeguard the endogenous neuron survival indicate that this cell source has a high clinical relevance for stroke therapy. ADSCs are known to ameliorate stroke symptoms by direct cell replacement, angiogenesis, enhanced immunosuppression, and an increase of the viability of endogenous neurons [45,46]. However, more research is usually required to improve the effectiveness of transplanted ADSCs as a treatment for stroke and other neurodegenerative diseases. Endodermal Potential of ADSCs According to the current literature, ADSCs can also differentiate into the endodermal lineage and therewith complete the tri-germ lineage potential. Some examples of the hepatic and pancreatic differentiation.