Journal
STEM CELL RESEARCH
Volume 15, Issue 2, Pages 341-353Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.scr.2015.07.001
Keywords
hNSC; SCI; Stem cell niche dynamics; Stem cell transplantation; Cell dose; Survival; Proliferation; Migration
Funding
- National Institutes of Health [U01NS079420]
- Christopher Reeve Foundation [AAC-2005]
- CIRM Postdoctoral Training Grant [TG2-01152]
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The effect of transplantation dose on the spatiotemporal dynamics of human neural stem cell (hNSC) engraftment has not been quantitatively evaluated in the central nervous system. We investigated changes over time in engraftment/survival, proliferation, and migration of multipotent human central nervous system-derived neural stem cells (hCNS-SCns) transplanted at doses ranging from 10,000 to 500,000 cells in spinal cord injured immunodeficient mice. Transplant dose was inversely correlated with measures of donor cell proliferation at 2 weeks post-transplant (WPT) and dose-normalized engraftment at 16 WPT. Critically, mice receiving the highest cell dose exhibited an engraftment plateau, in which the total number of engrafted human cells never exceeded the initial dose. These data suggest that donor cell expansion was inversely regulated by target niche parameters and/or transplantation density. Investigation of the response of donor cells to the host microenvironment should be a key variable in defining target cell dose in pre-clinical models of CNS disease and injury. Published by Elsevier B.V.
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