期刊
STEM CELLS TRANSLATIONAL MEDICINE
卷 7, 期 11, 页码 806-818出版社
WILEY
DOI: 10.1002/sctm.17-0269
关键词
Stem cells; Spinal cord injury; Oligodendrogenic neural progenitor cells; Remyelination; Regeneration; Oligodendrocytes
资金
- Industry Sponsored Collaborative Research Grant with New World Laboratories, Inc.
- New World Laboratories, Inc.
- Canadian Institutes of Health Research (CIHR)
- CIHR
- Gerry and Tootsie Halbert Chair in Neural Repair and Regeneration
- Dezwirek Foundation
- Krembil Foundation
Cell transplantation therapy utilizing neural precursor cells (NPCs) is a conceptually attractive strategy for traumatic spinal cord injury (SCI) to replace lost cells, remyelinate denuded host axons and promote tissue sparing. However, the number of mature oligodendrocytes that differentiate from typical NPCs remains limited. Herein, we describe a novel approach to bias the differentiation of directly reprogrammed human NPCs (drNPCs) toward a more oligodendrogenic fate (oNPCs) while preserving their tripotency. The oNPCs derived from different lines of human NPCs showed similar characteristics in vitro. To assess the in vivo efficacy of this approach, we used oNPCs derived from drNPCs and transplanted them into a SCI model in immunodeficient Rowett Nude (RNU) rats. The transplanted cells showed significant migration along the rostrocaudal axis and proportionally greater differentiation into oligodendrocytes. These cells promoted perilesional tissue sparing and axonal remyelination, which resulted in recovery of motor function. Moreover, after transplantation of the oNPCs into intact spinal cords of immunodeficient NOD/SCID mice, we detected no evidence of tumor formation even after 5 months of observation. Thus, biasing drNPC differentiation along an oligodendroglial lineage represents a promising approach to promote tissue sparing, axonal remyelination, and neural repair after traumatic SCI. Stem Cells Translational Medicine 2018;7:806-818
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