Stem cell survival and functional outcome after traumatic brain injury is dependent on transplant timing and location

Deborah A. Shear, Ciara C. Tate, Matthew C. Tate, David R. Archer, Michelle C. Laplaca, Donald G. Stein, Gary L. Dunbar

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Purpose: Recent work indicates that transplanted neural stem cells (NSCs) can survive, migrate to the injury site, and facilitate recovery from traumatic brain injury (TBI). The present study manipulated timing and location of NSC transplants following controlled cortical impact injury (CCI) in mice to determine optimal transplant conditions. Methods: In Experiment 1 (timing), NSCs (E14.5 mouse) were injected into the host striatum, ipsilateral to the injury, at 2, 7, or 14 days. In Experiment 2 (location), NSCs or vehicle were injected into the mouse striatum (7 days post-CCI) either ipsilateral or contralateral to the injury and cognitive and motor abilities were assessed from weeks 1-8 post-transplant. Histological measures of NSC survival, migration, and differentiation were taken at 6 and 8 weeks post-transplant. Results: The results demonstrate that: (1) 2-7 days post-injury is the optimal time-range for delivering NSCs; (2) time of transplantation does not affect short-term phenotypic differentiation; (3) transplant location affects survival, migration, phenotype, and functional efficacy; and (4) NSC-mediated functional recovery is not contingent upon NSC migration or phenotypic differentiation. Conclusions: These findings provide further support for the idea that mechanisms other than the replacement of damaged neurons or glia, such as NSC-induced increases in protective neurotrophic factors, may be responsible for the functional recovery observed in this model of TBI.

Original languageEnglish
Pages (from-to)215-225
Number of pages11
JournalRestorative Neurology and Neuroscience
Volume29
Issue number4
DOIs
StatePublished - 2011

Keywords

  • CNS repair
  • motor recovery
  • neural stem cells
  • spatial learning and memory
  • stem cell survival and migration
  • traumatic brain injury

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