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Applications of induced pluripotent stem cell technologies in spinal cord injury
Author(s) -
Nagoshi Narihito,
Okano Hideyuki
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13986
Subject(s) - induced pluripotent stem cell , spinal cord injury , neuroscience , embryonic stem cell , transplantation , regenerative medicine , neural stem cell , somatic cell , regeneration (biology) , stem cell , epigenetics , medicine , biology , neuroprotection , spinal cord , microbiology and biotechnology , genetics , gene
Numerous basic research studies have suggested the potential efficacy of neural precursor cell ( NPC ) transplantation in spinal cord injury ( SCI ). However, in most such studies, the origin of the cells used was mainly fetal tissue or embryonic stem cells, both of which carry potential ethical concerns with respect to clinical use. The development of induced pluripotent stem cells ( iPSC s) opened a new path toward regenerative medicine for SCI . iPSC s can be generated from somatic cells by induction of transcription factors, and induced to differentiate into NPC s with characteristics of cells of the central nervous system. The beneficial effect of iPSC ‐derived NPC transplantation has been reported from our group and others working in rodent and non‐human primate models. These promising results facilitate the application of iPSC s for clinical applications in SCI patients. However, iPSC s also have issues, such as genetic/epigenetic abnormalities and tumorigenesis because of the artificial induction method, that must be addressed prior to clinical use. The selection of somatic cells, generation of integration‐free iPSC s, and characterization of differentiated NPC s with thorough quality management are all needed to address these potential risks. To enhance the efficacy of the transplanted iPSC ‐ NPC s, especially at chronic phase of SCI , administration of a chondroitinase or semaphorin3A inhibitor represents a potentially important means of promoting axonal regeneration through the lesion site. The combined use of rehabilitation with such cell therapy approaches is also important, as repetitive training enhances neurite outgrowth of transplanted cells and strengthens neural circuits at central pattern generators. Our group has already evaluated clinical grade iPSC ‐derived NPC s, and we look forward to initiating clinical testing as the next step toward determining whether this approach is safe and effective for clinical use. This article is part of the mini review series “60th Anniversary of the Japanese Society for Neurochemistry” .