Neural progenitor cell transplants promote long-term functional recovery after traumatic brain injury

Deborah A. Shear, Matthew C. Tate, David R. Archer, Stuart W. Hoffman, Verne D. Hulce, Michelle C. Laplaca, Donald G. Stein

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

Studies demonstrating the versatility of neural progenitor cells (NPCs) have recently rekindled interest in neurotransplantation methods aimed at treating traumatic brain injury (TBI). However, few studies have evaluated the safety and functional efficacy of transplanted NPCs beyond a few months. The purpose of this study was to assess the long-term survival, migration, differentiation and functional significance of NPCs transplanted into a mouse model of TBI out to 1 year post-transplant. NPCs were derived from E14.5 mouse brains containing a transgene-expressing green fluorescent protein (GFP) and cultured as neurospheres in FGF2-containing medium. Neurospheres were injected into the ipsilateral striatum of adult C57BL/6 mice 1 week following unilateral cortical impact injury. Behavioral testing revealed significant improvements in motor abilities in NPC-treated mice as early as 1 week, and the recovery was sustained out to 1 year post-transplant. In addition, mice receiving NPC transplants showed significant improvement in spatial learning abilities at 3 months and 1 year, whereas an intermediate treatment effect on this behavioral parameter was detected at 1 month. At 14 months post-transplant, GFP + NPCs were observed throughout the injured hippocampus and adjacent cortical regions of transplanted brains. Immunohistochemical analysis revealed that the majority of transplanted cells co-labeled for NG2, an oligodendrocyte progenitor cell marker, but not for neuronal, astrocytic or microglial markers. In conclusion, transplanted NPCs survive in the host brain up to 14 months, migrate to the site of injury, enhance motor and cognitive recovery, and may play a role in trophic support following TBI.

Original languageEnglish (US)
Pages (from-to)11-22
Number of pages12
JournalBrain research
Volume1026
Issue number1
DOIs
StatePublished - Nov 5 2004

Fingerprint

Stem Cells
Transplants
Green Fluorescent Proteins
Brain
Traumatic Brain Injury
Aptitude
Oligodendroglia
Wounds and Injuries
Fibroblast Growth Factor 2
Transgenes
Inbred C57BL Mouse
Hippocampus
Safety

Keywords

  • Morris water maze
  • NG2
  • Neural stem cell
  • Neurosphere
  • Oligodendrocyte progenitor cell
  • Rotorod
  • Spatial learning
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Shear, D. A., Tate, M. C., Archer, D. R., Hoffman, S. W., Hulce, V. D., Laplaca, M. C., & Stein, D. G. (2004). Neural progenitor cell transplants promote long-term functional recovery after traumatic brain injury. Brain research, 1026(1), 11-22. https://doi.org/10.1016/j.brainres.2004.07.087
Shear, Deborah A. ; Tate, Matthew C. ; Archer, David R. ; Hoffman, Stuart W. ; Hulce, Verne D. ; Laplaca, Michelle C. ; Stein, Donald G. / Neural progenitor cell transplants promote long-term functional recovery after traumatic brain injury. In: Brain research. 2004 ; Vol. 1026, No. 1. pp. 11-22.
@article{d7bdd0ba048043d4afc8482cc2242ebf,
title = "Neural progenitor cell transplants promote long-term functional recovery after traumatic brain injury",
abstract = "Studies demonstrating the versatility of neural progenitor cells (NPCs) have recently rekindled interest in neurotransplantation methods aimed at treating traumatic brain injury (TBI). However, few studies have evaluated the safety and functional efficacy of transplanted NPCs beyond a few months. The purpose of this study was to assess the long-term survival, migration, differentiation and functional significance of NPCs transplanted into a mouse model of TBI out to 1 year post-transplant. NPCs were derived from E14.5 mouse brains containing a transgene-expressing green fluorescent protein (GFP) and cultured as neurospheres in FGF2-containing medium. Neurospheres were injected into the ipsilateral striatum of adult C57BL/6 mice 1 week following unilateral cortical impact injury. Behavioral testing revealed significant improvements in motor abilities in NPC-treated mice as early as 1 week, and the recovery was sustained out to 1 year post-transplant. In addition, mice receiving NPC transplants showed significant improvement in spatial learning abilities at 3 months and 1 year, whereas an intermediate treatment effect on this behavioral parameter was detected at 1 month. At 14 months post-transplant, GFP + NPCs were observed throughout the injured hippocampus and adjacent cortical regions of transplanted brains. Immunohistochemical analysis revealed that the majority of transplanted cells co-labeled for NG2, an oligodendrocyte progenitor cell marker, but not for neuronal, astrocytic or microglial markers. In conclusion, transplanted NPCs survive in the host brain up to 14 months, migrate to the site of injury, enhance motor and cognitive recovery, and may play a role in trophic support following TBI.",
keywords = "Morris water maze, NG2, Neural stem cell, Neurosphere, Oligodendrocyte progenitor cell, Rotorod, Spatial learning, Traumatic brain injury",
author = "Shear, {Deborah A.} and Tate, {Matthew C.} and Archer, {David R.} and Hoffman, {Stuart W.} and Hulce, {Verne D.} and Laplaca, {Michelle C.} and Stein, {Donald G.}",
year = "2004",
month = "11",
day = "5",
doi = "10.1016/j.brainres.2004.07.087",
language = "English (US)",
volume = "1026",
pages = "11--22",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "1",

}

Neural progenitor cell transplants promote long-term functional recovery after traumatic brain injury. / Shear, Deborah A.; Tate, Matthew C.; Archer, David R.; Hoffman, Stuart W.; Hulce, Verne D.; Laplaca, Michelle C.; Stein, Donald G.

In: Brain research, Vol. 1026, No. 1, 05.11.2004, p. 11-22.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Neural progenitor cell transplants promote long-term functional recovery after traumatic brain injury

AU - Shear, Deborah A.

AU - Tate, Matthew C.

AU - Archer, David R.

AU - Hoffman, Stuart W.

AU - Hulce, Verne D.

AU - Laplaca, Michelle C.

AU - Stein, Donald G.

PY - 2004/11/5

Y1 - 2004/11/5

N2 - Studies demonstrating the versatility of neural progenitor cells (NPCs) have recently rekindled interest in neurotransplantation methods aimed at treating traumatic brain injury (TBI). However, few studies have evaluated the safety and functional efficacy of transplanted NPCs beyond a few months. The purpose of this study was to assess the long-term survival, migration, differentiation and functional significance of NPCs transplanted into a mouse model of TBI out to 1 year post-transplant. NPCs were derived from E14.5 mouse brains containing a transgene-expressing green fluorescent protein (GFP) and cultured as neurospheres in FGF2-containing medium. Neurospheres were injected into the ipsilateral striatum of adult C57BL/6 mice 1 week following unilateral cortical impact injury. Behavioral testing revealed significant improvements in motor abilities in NPC-treated mice as early as 1 week, and the recovery was sustained out to 1 year post-transplant. In addition, mice receiving NPC transplants showed significant improvement in spatial learning abilities at 3 months and 1 year, whereas an intermediate treatment effect on this behavioral parameter was detected at 1 month. At 14 months post-transplant, GFP + NPCs were observed throughout the injured hippocampus and adjacent cortical regions of transplanted brains. Immunohistochemical analysis revealed that the majority of transplanted cells co-labeled for NG2, an oligodendrocyte progenitor cell marker, but not for neuronal, astrocytic or microglial markers. In conclusion, transplanted NPCs survive in the host brain up to 14 months, migrate to the site of injury, enhance motor and cognitive recovery, and may play a role in trophic support following TBI.

AB - Studies demonstrating the versatility of neural progenitor cells (NPCs) have recently rekindled interest in neurotransplantation methods aimed at treating traumatic brain injury (TBI). However, few studies have evaluated the safety and functional efficacy of transplanted NPCs beyond a few months. The purpose of this study was to assess the long-term survival, migration, differentiation and functional significance of NPCs transplanted into a mouse model of TBI out to 1 year post-transplant. NPCs were derived from E14.5 mouse brains containing a transgene-expressing green fluorescent protein (GFP) and cultured as neurospheres in FGF2-containing medium. Neurospheres were injected into the ipsilateral striatum of adult C57BL/6 mice 1 week following unilateral cortical impact injury. Behavioral testing revealed significant improvements in motor abilities in NPC-treated mice as early as 1 week, and the recovery was sustained out to 1 year post-transplant. In addition, mice receiving NPC transplants showed significant improvement in spatial learning abilities at 3 months and 1 year, whereas an intermediate treatment effect on this behavioral parameter was detected at 1 month. At 14 months post-transplant, GFP + NPCs were observed throughout the injured hippocampus and adjacent cortical regions of transplanted brains. Immunohistochemical analysis revealed that the majority of transplanted cells co-labeled for NG2, an oligodendrocyte progenitor cell marker, but not for neuronal, astrocytic or microglial markers. In conclusion, transplanted NPCs survive in the host brain up to 14 months, migrate to the site of injury, enhance motor and cognitive recovery, and may play a role in trophic support following TBI.

KW - Morris water maze

KW - NG2

KW - Neural stem cell

KW - Neurosphere

KW - Oligodendrocyte progenitor cell

KW - Rotorod

KW - Spatial learning

KW - Traumatic brain injury

UR - http://www.scopus.com/inward/record.url?scp=5044222203&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=5044222203&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2004.07.087

DO - 10.1016/j.brainres.2004.07.087

M3 - Article

VL - 1026

SP - 11

EP - 22

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1

ER -