Regenerative Medicine in the Central Nervous System: Stem Cell-Based Cell- and Gene-Therapy

Abstract

Human neurological diseases such as Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), multiple sclerosis (MS), stroke and spinal cord injury are caused by a loss of neurons and glial cells in the brain or spinal cord. Cell replacement therapy and gene transfer to the diseased or injured brain have provided the basis for the development of potentially powerful new therapeutic strategies for a broad spectrum of human neurological diseases. However, the paucity of suitable cell types for cell replacement therapy in patients suffering from neurological disorders has hampered the development of this promising therapeutic approach. In recent years, neurons and glial cells have successfully been generated from stem cells such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs) and neural stem cells (NSCs), and extensive efforts by investigators to develop stem cell-based brain transplantation therapies have been carried out. I review here notable experimental and pre-clinical studies previously published involving stem cell-based cell- and gene-therapies for PD, HD, ALS, AD, MS and stroke, and discuss for future prospect for the stem cell therapy of neurological disorders in clinical setting. There are still many obstacles to be overcome before clinical application of cell- and gene-therapy in neurological disease patients is adopted: (i) it is still uncertain how to generate specific cell types of neurons or glia suitable for cellular grafts in great quantity, (ii) it is required to abate safety concern related to tumor formation following NSC transplantation, and (iii) it needs to be better understood by what mechanism transplantation of NSCs leads to an enhanced functional recovery. Steady and stepwise progress in stem cell research in both basic and pre-clinical settings should support the hope for development of stem cell-based therapies for neurodegenerative diseases. This review focuses on the utility of stem cells particularly NSCs as substrates for structural and functional repair of the diseased or injured brain.