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Transl Stroke Res. 2019 Feb 12. doi: 10.1007/s12975-019-0691-x. [Epub ahead of print]

Transplantation of Directly Reprogrammed Human Neural Precursor Cells Following Stroke Promotes Synaptogenesis and Functional Recovery.

Author information

1
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, M5S 3E1, Canada.
2
Institute of Medical Science, University of Toronto, Toronto, Ontario, M5S 3E1, Canada.
3
Department of Surgery, Division of Anatomy, Donnelly Centre, University of Toronto, Toronto, Ontario, M5S 3E1, Canada.
4
New World Laboratories, Laval, Quebec, H7V 5B7, Canada.
5
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, M5S 3E1, Canada. cindi.morshead@utoronto.ca.
6
Institute of Medical Science, University of Toronto, Toronto, Ontario, M5S 3E1, Canada. cindi.morshead@utoronto.ca.
7
Department of Surgery, Division of Anatomy, Donnelly Centre, University of Toronto, Toronto, Ontario, M5S 3E1, Canada. cindi.morshead@utoronto.ca.

Abstract

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.

KEYWORDS:

Cell reprogramming; Functional recovery; Stem cells; Synaptogenesis; Transplantation

PMID:
30747366
DOI:
10.1007/s12975-019-0691-x

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