Journal
TRANSLATIONAL STROKE RESEARCH
Volume 11, Issue 1, Pages 93-107Publisher
SPRINGER
DOI: 10.1007/s12975-019-0691-x
Keywords
Transplantation; Stem cells; Cell reprogramming; Synaptogenesis; Functional recovery
Categories
Funding
- Canadian Institutes of Health Research (CIHR)
- New World Laboratories Inc.
- Canada First Research Excellent Fund (CFREF, Medicine by Design)
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Stroke is one of the leading causes of long-term disability. Cell transplantation is a promising strategy to treat stroke. We explored the efficacy of directly reprogrammed human neural precursor cell (drNPC) transplants to promote functional recovery in a model of focal ischemic stroke in the mouse sensorimotor cortex. We show that drNPCs express neural precursor cell markers and are neurally committed at the time of transplantation. Mice that received drNPC transplants recovered motor function, irrespective of transplant vehicle or recipient sex, and with no correlation to lesion volume or glial scarring. The majority of drNPCs found in vivo, at the time of functional recovery, remained undifferentiated. Notably, no correlation between functional recovery and long-term xenograft survival was observed, indicating that drNPCs provide therapeutic benefits beyond their survival. Furthermore, increased synaptophysin expression in transplanted brains suggests that drNPCs promote neuroplasticity through enhanced synaptogenesis. Our findings provide insight into the mechanistic underpinnings of drNPC-mediated recovery for stroke and support the notion that drNPCs may have clinical applications for stroke therapy.
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