Human fetal neural stem cells grafted into contusion-injured rat spinal cords improve behavior

Yevgeniya I. Tarasenko, Junling Gao, Linghui Nie, Kathia M. Johnson, James J. Grady, Claire E. Hulsebosch, David J. McAdoo, Ping Wu

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Grafted human neural stem cells (hNSCs) may help to alleviate functional deficits resulting from spinal cord injury by bridging gaps, replacing lost neurons or oligodendrocytes, and providing neurotrophic factors. Previously, we showed that primed hNSCs differentiated into cholinergic neurons in an intact spinal cord. In this study, we tested the fate of hNSCs transplanted into a spinal cord T10 contusion injury model. When grafted into injured spinal cords of adult male rats on either the same day or 3 or 9 days after a moderate contusion injury, both primed and unprimed hNSCs survived for 3 months postengraftment only in animals that received grafts at 9 days postinjury. Histological analyses revealed that primed hNSCs tended to survive better and differentiated at higher rates into neurons and oligodendrocytes than did unprimed counterparts. Furthermore, only primed cells gave rise to cholinergic neurons. Animals receiving primed hNSC grafts on the ninth day postcontusion improved trunk stability, as determined by rearing activity measurements 3 months after grafting. This study indicates that human neural stem cell fate determination in vivo is influenced by the predifferentiation stage of stem cells prior to grafting. Furthermore, stem cell-mediated facilitation of functional improvement depends on the timing of transplantation after injury, the grafting sites, and the survival of newly differentiated neurons and oligodendrocytes.

Original languageEnglish (US)
Pages (from-to)47-57
Number of pages11
JournalJournal of Neuroscience Research
Volume85
Issue number1
DOIs
StatePublished - Jan 2007

Fingerprint

Fetal Stem Cells
Neural Stem Cells
Contusions
Spinal Cord
Oligodendroglia
Cholinergic Neurons
Spinal Cord Injuries
Neurons
Wounds and Injuries
Stem Cells
Transplants
Nerve Growth Factors
Transplantation
Survival

Keywords

  • Cell therapy
  • Cholinergic neurons
  • Differentiation
  • Transplantation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Human fetal neural stem cells grafted into contusion-injured rat spinal cords improve behavior. / Tarasenko, Yevgeniya I.; Gao, Junling; Nie, Linghui; Johnson, Kathia M.; Grady, James J.; Hulsebosch, Claire E.; McAdoo, David J.; Wu, Ping.

In: Journal of Neuroscience Research, Vol. 85, No. 1, 01.2007, p. 47-57.

Research output: Contribution to journalArticle

Tarasenko, YI, Gao, J, Nie, L, Johnson, KM, Grady, JJ, Hulsebosch, CE, McAdoo, DJ & Wu, P 2007, 'Human fetal neural stem cells grafted into contusion-injured rat spinal cords improve behavior', Journal of Neuroscience Research, vol. 85, no. 1, pp. 47-57. https://doi.org/10.1002/jnr.21098
Tarasenko, Yevgeniya I. ; Gao, Junling ; Nie, Linghui ; Johnson, Kathia M. ; Grady, James J. ; Hulsebosch, Claire E. ; McAdoo, David J. ; Wu, Ping. / Human fetal neural stem cells grafted into contusion-injured rat spinal cords improve behavior. In: Journal of Neuroscience Research. 2007 ; Vol. 85, No. 1. pp. 47-57.
@article{109420cb94924f6696d69425ff7f9c91,
title = "Human fetal neural stem cells grafted into contusion-injured rat spinal cords improve behavior",
abstract = "Grafted human neural stem cells (hNSCs) may help to alleviate functional deficits resulting from spinal cord injury by bridging gaps, replacing lost neurons or oligodendrocytes, and providing neurotrophic factors. Previously, we showed that primed hNSCs differentiated into cholinergic neurons in an intact spinal cord. In this study, we tested the fate of hNSCs transplanted into a spinal cord T10 contusion injury model. When grafted into injured spinal cords of adult male rats on either the same day or 3 or 9 days after a moderate contusion injury, both primed and unprimed hNSCs survived for 3 months postengraftment only in animals that received grafts at 9 days postinjury. Histological analyses revealed that primed hNSCs tended to survive better and differentiated at higher rates into neurons and oligodendrocytes than did unprimed counterparts. Furthermore, only primed cells gave rise to cholinergic neurons. Animals receiving primed hNSC grafts on the ninth day postcontusion improved trunk stability, as determined by rearing activity measurements 3 months after grafting. This study indicates that human neural stem cell fate determination in vivo is influenced by the predifferentiation stage of stem cells prior to grafting. Furthermore, stem cell-mediated facilitation of functional improvement depends on the timing of transplantation after injury, the grafting sites, and the survival of newly differentiated neurons and oligodendrocytes.",
keywords = "Cell therapy, Cholinergic neurons, Differentiation, Transplantation",
author = "Tarasenko, {Yevgeniya I.} and Junling Gao and Linghui Nie and Johnson, {Kathia M.} and Grady, {James J.} and Hulsebosch, {Claire E.} and McAdoo, {David J.} and Ping Wu",
year = "2007",
month = "1",
doi = "10.1002/jnr.21098",
language = "English (US)",
volume = "85",
pages = "47--57",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Human fetal neural stem cells grafted into contusion-injured rat spinal cords improve behavior

AU - Tarasenko, Yevgeniya I.

AU - Gao, Junling

AU - Nie, Linghui

AU - Johnson, Kathia M.

AU - Grady, James J.

AU - Hulsebosch, Claire E.

AU - McAdoo, David J.

AU - Wu, Ping

PY - 2007/1

Y1 - 2007/1

N2 - Grafted human neural stem cells (hNSCs) may help to alleviate functional deficits resulting from spinal cord injury by bridging gaps, replacing lost neurons or oligodendrocytes, and providing neurotrophic factors. Previously, we showed that primed hNSCs differentiated into cholinergic neurons in an intact spinal cord. In this study, we tested the fate of hNSCs transplanted into a spinal cord T10 contusion injury model. When grafted into injured spinal cords of adult male rats on either the same day or 3 or 9 days after a moderate contusion injury, both primed and unprimed hNSCs survived for 3 months postengraftment only in animals that received grafts at 9 days postinjury. Histological analyses revealed that primed hNSCs tended to survive better and differentiated at higher rates into neurons and oligodendrocytes than did unprimed counterparts. Furthermore, only primed cells gave rise to cholinergic neurons. Animals receiving primed hNSC grafts on the ninth day postcontusion improved trunk stability, as determined by rearing activity measurements 3 months after grafting. This study indicates that human neural stem cell fate determination in vivo is influenced by the predifferentiation stage of stem cells prior to grafting. Furthermore, stem cell-mediated facilitation of functional improvement depends on the timing of transplantation after injury, the grafting sites, and the survival of newly differentiated neurons and oligodendrocytes.

AB - Grafted human neural stem cells (hNSCs) may help to alleviate functional deficits resulting from spinal cord injury by bridging gaps, replacing lost neurons or oligodendrocytes, and providing neurotrophic factors. Previously, we showed that primed hNSCs differentiated into cholinergic neurons in an intact spinal cord. In this study, we tested the fate of hNSCs transplanted into a spinal cord T10 contusion injury model. When grafted into injured spinal cords of adult male rats on either the same day or 3 or 9 days after a moderate contusion injury, both primed and unprimed hNSCs survived for 3 months postengraftment only in animals that received grafts at 9 days postinjury. Histological analyses revealed that primed hNSCs tended to survive better and differentiated at higher rates into neurons and oligodendrocytes than did unprimed counterparts. Furthermore, only primed cells gave rise to cholinergic neurons. Animals receiving primed hNSC grafts on the ninth day postcontusion improved trunk stability, as determined by rearing activity measurements 3 months after grafting. This study indicates that human neural stem cell fate determination in vivo is influenced by the predifferentiation stage of stem cells prior to grafting. Furthermore, stem cell-mediated facilitation of functional improvement depends on the timing of transplantation after injury, the grafting sites, and the survival of newly differentiated neurons and oligodendrocytes.

KW - Cell therapy

KW - Cholinergic neurons

KW - Differentiation

KW - Transplantation

UR - http://www.scopus.com/inward/record.url?scp=33846157139&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846157139&partnerID=8YFLogxK

U2 - 10.1002/jnr.21098

DO - 10.1002/jnr.21098

M3 - Article

VL - 85

SP - 47

EP - 57

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 1

ER -