Human mesenchymal stem cells prolong survival and ameliorate motor deficit through trophic support in Huntington's disease mouse models

Yuan Ta Lin, Yijuang Chern, Che Kun James Shen, Hsin Lan Wen, Ya Chin Chang, Hung Li, Tzu Hao Cheng, Hsiu Mei Hsieh-Li

Research output: Contribution to journalArticle

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Abstract

We investigated the therapeutic potential of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in Huntington's disease (HD) mouse models. Ten weeks after intrastriatal injection of quinolinic acid (QA), mice that received hBM-MSC transplantation showed a significant reduction in motor function impairment and increased survival rate. Transplanted hBM-MSCs were capable of survival, and inducing neural proliferation and differentiation in the QA-lesioned striatum. In addition, the transplanted hBM-MSCs induced microglia, neuroblasts and bone marrow-derived cells to migrate into the QA-lesioned region. Similar results were obtained in R6/2-J2, a genetically-modified animal model of HD, except for the improvement of motor function. After hBM-MSC transplantation, the transplanted hBM-MSCs may integrate with the host cells and increase the levels of laminin, Von Willebrand Factor (VWF), stromal cell-derived factor-1 (SDF-1), and the SDF-1 receptor Cxcr4. The p-Erk1/2 expression was increased while Bax and caspase-3 levels were decreased after hBM-MSC transplantation suggesting that the reduced level of apoptosis after hBM-MSC transplantation was of benefit to the QA-lesioned mice. Our data suggest that hBM-MSCs have neural differentiation improvement potential, neurotrophic support capability and an anti-apoptotic effect, and may be a feasible candidate for HD therapy.

Original languageEnglish
Article numbere22924
JournalPloS one
Volume6
Issue number8
DOIs
Publication statusPublished - 2011 Aug 10

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disease models
Huntington Disease
Stem cells
Mesenchymal Stromal Cells
bone marrow
cell viability
stem cells
Cell Survival
Bone
animal models
Bone Marrow
Mesenchymal Stem Cell Transplantation
Quinolinic Acid
cell transplantation
Chemokine CXCL12
acids
animal disease models
Genetically Modified Animals
therapeutics
blood coagulation factors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Human mesenchymal stem cells prolong survival and ameliorate motor deficit through trophic support in Huntington's disease mouse models. / Lin, Yuan Ta; Chern, Yijuang; Shen, Che Kun James; Wen, Hsin Lan; Chang, Ya Chin; Li, Hung; Cheng, Tzu Hao; Hsieh-Li, Hsiu Mei.

In: PloS one, Vol. 6, No. 8, e22924, 10.08.2011.

Research output: Contribution to journalArticle

Lin, Yuan Ta ; Chern, Yijuang ; Shen, Che Kun James ; Wen, Hsin Lan ; Chang, Ya Chin ; Li, Hung ; Cheng, Tzu Hao ; Hsieh-Li, Hsiu Mei. / Human mesenchymal stem cells prolong survival and ameliorate motor deficit through trophic support in Huntington's disease mouse models. In: PloS one. 2011 ; Vol. 6, No. 8.
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