Human neural stem cell transplants improve motor function in a rat model of Huntington's disease

Jodi McBride, Soshana P. Behrstock, Er Yun Chen, Rebekah J. Jakel, Irwin Siegel, Clive N. Svendsen, Jeffrey H. Kordower

Research output: Contribution to journalArticle

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Abstract

The present study investigated the neuroanatomical and behavioral effects of human stem cell transplants into the striatum of quinolinic acid (QA)-lesioned rats. Twenty-four rats received unilateral QA (200 nM/μl) injections into the striatum. One week later, rats were transplanted with stem cells derived from human fetal cortex (12 weeks postconception) that were either 1) pretreated in culture media with the differentiating cytokine ciliary neurotrophic factor (CNTF; n = 9) or 2) allowed to grow in culture media alone (n = 7). Each rat was injected with a total of 200,000 cells. A third group of rats (n = 8) was given a sham injection of vehicle. Rats transplanted with human stem cells performed significantly better over the 8 weeks of testing on the cylinder test compared with those treated with vehicle (P ≤ 0.001). Stereological striatal volume analyses performed on Nissl-stained sections revealed that rats transplanted with CNTF-treated neurospheres had a 22% greater striatal volume on the lesioned side compared with those receiving transplants of untreated neurospheres (P = 0.0003) and a 26% greater striatal volume compared with rats injected with vehicle (P ≤ 0.0001). Numerous human nuclei-positive cells were visualized in the striatum in both transplantation groups. Grafted cells were also observed in the globus pallidus, entopeduncular nucleus, and substantia nigra pars reticulata, areas of the basal ganglia receiving striatal projections. Some of the human nuclei-positive cells coexpressed glial fibrillary acidic protein and NeuN, suggesting that they had differentiated into neurons and astrocytes. Taken together, these data demonstrate that striatal transplants of human fetal stem cells elicit behavioral and anatomical recovery in a rodent model of Huntington's disease.

Original languageEnglish (US)
Pages (from-to)211-219
Number of pages9
JournalJournal of Comparative Neurology
Volume475
Issue number2
DOIs
StatePublished - Jul 19 2004
Externally publishedYes

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Neural Stem Cells
Huntington Disease
Corpus Striatum
Transplants
Ciliary Neurotrophic Factor
Quinolinic Acid
Stem Cells
Cell Nucleus
Culture Media
Entopeduncular Nucleus
Fetal Stem Cells
Injections
Globus Pallidus
Glial Fibrillary Acidic Protein
Basal Ganglia
Astrocytes
Rodentia
Transplantation
Cytokines
Neurons

Keywords

  • Differentiation
  • Human neurospheres
  • Migration
  • Proliferation
  • Quinolinic acid
  • Xenograft

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

McBride, J., Behrstock, S. P., Chen, E. Y., Jakel, R. J., Siegel, I., Svendsen, C. N., & Kordower, J. H. (2004). Human neural stem cell transplants improve motor function in a rat model of Huntington's disease. Journal of Comparative Neurology, 475(2), 211-219. https://doi.org/10.1002/cne.20176

Human neural stem cell transplants improve motor function in a rat model of Huntington's disease. / McBride, Jodi; Behrstock, Soshana P.; Chen, Er Yun; Jakel, Rebekah J.; Siegel, Irwin; Svendsen, Clive N.; Kordower, Jeffrey H.

In: Journal of Comparative Neurology, Vol. 475, No. 2, 19.07.2004, p. 211-219.

Research output: Contribution to journalArticle

McBride, J, Behrstock, SP, Chen, EY, Jakel, RJ, Siegel, I, Svendsen, CN & Kordower, JH 2004, 'Human neural stem cell transplants improve motor function in a rat model of Huntington's disease', Journal of Comparative Neurology, vol. 475, no. 2, pp. 211-219. https://doi.org/10.1002/cne.20176
McBride, Jodi ; Behrstock, Soshana P. ; Chen, Er Yun ; Jakel, Rebekah J. ; Siegel, Irwin ; Svendsen, Clive N. ; Kordower, Jeffrey H. / Human neural stem cell transplants improve motor function in a rat model of Huntington's disease. In: Journal of Comparative Neurology. 2004 ; Vol. 475, No. 2. pp. 211-219.
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