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

*Corresponding author for this work

Research output: Contribution to journalArticle

36 Citations (Scopus)

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 (US)
Pages (from-to)215-225
Number of pages11
JournalRestorative Neurology and Neuroscience
Volume29
Issue number4
DOIs
StatePublished - Aug 15 2011

Fingerprint

Neural Stem Cells
Cell Survival
Stem Cells
Transplants
Wounds and Injuries
Cell Movement
Traumatic Brain Injury
Nerve Growth Factors
Neuroglia
Cell Differentiation
Transplantation
Phenotype
Neurons

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Clinical Neurology

Cite this

Shear, Deborah A. ; Tate, Ciara C. ; Tate, Matthew C. ; Archer, David R. ; Laplaca, Michelle C. ; Stein, Donald G. ; Dunbar, Gary L. / Stem cell survival and functional outcome after traumatic brain injury is dependent on transplant timing and location. In: Restorative Neurology and Neuroscience. 2011 ; Vol. 29, No. 4. pp. 215-225.
@article{a531aaea3fc444c4b08a34e3b182b549,
title = "Stem cell survival and functional outcome after traumatic brain injury is dependent on transplant timing and location",
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.",
keywords = "CNS repair, motor recovery, neural stem cells, spatial learning and memory, stem cell survival and migration, traumatic brain injury",
author = "Shear, {Deborah A.} and Tate, {Ciara C.} and Tate, {Matthew C.} and Archer, {David R.} and Laplaca, {Michelle C.} and Stein, {Donald G.} and Dunbar, {Gary L.}",
year = "2011",
month = "8",
day = "15",
doi = "10.3233/RNN-2011-0593",
language = "English (US)",
volume = "29",
pages = "215--225",
journal = "Restorative Neurology and Neuroscience",
issn = "0922-6028",
publisher = "IOS Press",
number = "4",

}

Stem cell survival and functional outcome after traumatic brain injury is dependent on transplant timing and location. / Shear, Deborah A.; Tate, Ciara C.; Tate, Matthew C.; Archer, David R.; Laplaca, Michelle C.; Stein, Donald G.; Dunbar, Gary L.

In: Restorative Neurology and Neuroscience, Vol. 29, No. 4, 15.08.2011, p. 215-225.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Stem cell survival and functional outcome after traumatic brain injury is dependent on transplant timing and location

AU - Shear, Deborah A.

AU - Tate, Ciara C.

AU - Tate, Matthew C.

AU - Archer, David R.

AU - Laplaca, Michelle C.

AU - Stein, Donald G.

AU - Dunbar, Gary L.

PY - 2011/8/15

Y1 - 2011/8/15

N2 - 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.

AB - 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.

KW - CNS repair

KW - motor recovery

KW - neural stem cells

KW - spatial learning and memory

KW - stem cell survival and migration

KW - traumatic brain injury

UR - http://www.scopus.com/inward/record.url?scp=80051525020&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80051525020&partnerID=8YFLogxK

U2 - 10.3233/RNN-2011-0593

DO - 10.3233/RNN-2011-0593

M3 - Article

VL - 29

SP - 215

EP - 225

JO - Restorative Neurology and Neuroscience

JF - Restorative Neurology and Neuroscience

SN - 0922-6028

IS - 4

ER -