Preparation, characterization, and banking of clinical-grade cells for neural transplantation: Scale up, fingerprinting, and genomic stability of stem cell lines.

摘要: Parkinson's disease is a complex and progressive neurodegenerative condition that characterized by the severe loss of midbrain dopaminergic (mDA) neurons, which innervate striatum. Cell transplantation therapies to rebuild this network have been attempted for over 30 years. The most promising outcomes were observed when human fetal mesencephalic tissue was used as source cells transplantation. However, reliance on terminations therapy presents significant logistical ethical hurdles. An alternative transplantable mDA neurons urgently needed, solution may come from embryonic stem (hESCs) induced pluripotent (iPSCs). Protocols differentiate hESCs/iPSCs toward are now robust efficient, upon grafting rescue preclinical animal models disease. challenge apply Good Manufacturing Practice (GMP) academic discoveries protocols produce clinical-grade cells. Major technical considerations include (i) hESC or iPSC line, (ii) GMP compliance differentiation protocol all reagents, (iii) characterization cell product in terms identity, safety, efficacy, (iv) genomic state stability, (v) banking transplantation-ready product. Approaches solutions these challenges reviewed here.