Human pluripotent stem cells(PSCs)such as embryonic stem cells(ESCs)and induced pluripotent stem cells(iPSCs)hold great promise in regenerative medicine as they are an important source of functional cells for potential cell replacement.These human PSCs,similar to their counterparts of mouse,have the full potential to give rise to any type of cells in the body.However,for the promise to be fulfilled,it is necessary to convert these PSCs into functional specialized cells.Using the developmental principles of neural lineage specification,human ESCs and iPSCs have been effectively differentiated to regional and functional specific neurons and glia,such as striatal gama-aminobutyric acid(GABA)-ergic neurons,spinal motor neurons and myelin sheath forming oligodendrocytes.The human PSCs,in general differentiate after the similar developmental program as that of the mouse:they use the same set of cell signaling to tune the cell fate and they share a conserved transcriptional program that directs the cell fate transition.However,the human PSCs,unlike their counterparts of mouse,tend to respond divergently to the same set of extracellular signals at certain stages of differentiation,which will be a critical consideration to translate the animal model based studies to clinical application.
Objective: This study aimed to use a systematic approach to evaluate the current utilization, safety, and effectiveness of cell therapies for neurological diseases in human. And review the present regulations, considering United States(US) as a representative country, for cell transplantation in neurological disease and discuss the challenges facing the field of neurology in the coming decades. Methods: A detailed search was performed in systematic literature reviews of cellular‐based therapies in neurological diseases, using Pub Med, web of science, and clinical trials. Regulations of cell therapy products used for clinical trials were searched from the Food and Drug Administration(FDA) and the National Institutes of Health(NIH).Results: Seven most common types of cell therapies for neurological diseases have been reported to be relatively safe with varying degrees of neurological recovery.And a series of regulations in US for cellular therapy was summarized including preclinical evaluations, sourcing material, stem cell manufacturing and characterization,cell therapy product, and clinical trials. Conclusions: Stem cell‐based therapy holds great promise for a cure of such diseases and will value a growing population of patients. However, regulatory permitting activity of the US in the sphere of stem cells, technologies of regenerative medicine and substitutive cell therapy are selective, theoretical and does not fit the existing norm and rules. Compiled well‐defined regulations to guide the application of stem cell products for clinical trials should be formulated.
He ZhuYuanqing TanQi GuWeifang HanZhongwen LiJason S. MeyerBaoyang Hu
