Abstract:

Glypican 4 down-regulation in pluripotent stem cells as a potential strategy to improve differentiation and to impair tumorigenicity of cell transplants
Recent advances in stem cell technologies have opened new avenues for the treatment of a number of diseases that still lack effective therapeutic options. In this regard, cell transplantation has emerged as the most promising clinical medical intervention for the repair, replacement, and regeneration of dysfunctional or dead cells. Examples of specific disorders that might benefit from stem cell-based therapies are injuries, diabetes, liver and retinal diseases, neurological disorders and possibly heart failure. To date much attention has been given to the potential application of human pluripotent stem cells (hPSCs) including both embryonic (hESCs) and the induced pluripotent stem cells (hiPSCs) for regenerative medicine. Besides being considered particularly relevant for disease modeling, drug discovery and for pharmaceutical applications, extensive research is underway to determine whether hPSCs can become a potent and safe resource of transplantable therapeutics. Owing to their remarkable ability to self-renewal indefinitely and to differentiate into all mature cell types hPSCs would be of great advantage to generate an unlimited number of disease-relevant cells. From a clinical perspective, it is likely that hPSC-derivatives such as progenitor cells and/or more differentiated somatic cell types rather than the “bonafide” hPSCs will be transplanted. Although the risk of having tumor-promoting cells in grafts might be relatively low when transplanting small cell numbers (e.g., for retinal regeneration), the greatest challenge occurs when treating diseases requiring large quantities of hPSC-derived cells. Also, as knowledge on transplantation-based therapies will advance, new set of variables such as batch-to-batch differences in hPSC differentiation efficacy might arise. As discussed above, a variety of approaches are being developed to ensure that no self-renewing cells remain in the graft. However, there is an ongoing need to improve these methods in order to achieve realistic, cost effective and clinically applicable strategies. It will be important to evaluate whether the most stringent safety procedure arise from combining different technologies that can be shaped according to disease and cell graft needs.