RRC ID 12723
Author Tsuji O, Miura K, Okada Y, Fujiyoshi K, Mukaino M, Nagoshi N, Kitamura K, Kumagai G, Nishino M, Tomisato S, Higashi H, Nagai T, Katoh H, Kohda K, Matsuzaki Y, Yuzaki M, Ikeda E, Toyama Y, Nakamura M, Yamanaka S, Okano H.
Title Therapeutic potential of appropriately evaluated safe-induced pluripotent stem cells for spinal cord injury.
Journal Proc Natl Acad Sci U S A
Abstract Various types of induced pluripotent stem (iPS) cells have been established by different methods, and each type exhibits different biological properties. Before iPS cell-based clinical applications can be initiated, detailed evaluations of the cells, including their differentiation potentials and tumorigenic activities in different contexts, should be investigated to establish their safety and effectiveness for cell transplantation therapies. Here we show the directed neural differentiation of murine iPS cells and examine their therapeutic potential in a mouse spinal cord injury (SCI) model. "Safe" iPS-derived neurospheres, which had been pre-evaluated as nontumorigenic by their transplantation into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse brain, produced electrophysiologically functional neurons, astrocytes, and oligodendrocytes in vitro. Furthermore, when the safe iPS-derived neurospheres were transplanted into the spinal cord 9 d after contusive injury, they differentiated into all three neural lineages without forming teratomas or other tumors. They also participated in remyelination and induced the axonal regrowth of host 5HT(+) serotonergic fibers, promoting locomotor function recovery. However, the transplantation of iPS-derived neurospheres pre-evaluated as "unsafe" showed robust teratoma formation and sudden locomotor functional loss after functional recovery in the SCI model. These findings suggest that pre-evaluated safe iPS clone-derived neural stem/progenitor cells may be a promising cell source for transplantation therapy for SCI.
Volume 107(28)
Pages 12704-9
Published 2010-7-13
DOI 10.1073/pnas.0910106107
PII 0910106107
PMID 20615974
PMC PMC2906548
MeSH Animals Astrocytes / pathology Astrocytes / transplantation Axons / pathology Axons / transplantation Cell Differentiation / physiology Cell Transplantation Cells, Cultured Female Induced Pluripotent Stem Cells Mice Mice, Inbred C57BL Motor Activity / physiology Neurons / cytology Neurons / pathology Neurons / transplantation Oligodendroglia / cytology Oligodendroglia / physiology Oligodendroglia / transplantation Recovery of Function / physiology Regeneration Spinal Cord / cytology Spinal Cord / surgery Spinal Cord / transplantation Spinal Cord Injuries / pathology* Spinal Cord Injuries / physiopathology* Spinal Cord Injuries / surgery Stem Cells / pathology
IF 9.412
Times Cited 328
DNA material pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393)