Mesenchymal stem cell transplantation ameliorates motor function deterioration of spinocerebellar ataxia by rescuing cerebellar Purkinje cells
10.1186/1423-0127-18-54
Crossref journal-article
Springer Science and Business Media LLC
Journal of Biomedical Science (297)
Abstract

Abstract Background Spinocerebellar ataxia (SCA) refers to a disease entity in which polyglutamine aggregates are over-produced in Purkinje cells (PCs) of the cerebellum as well as other neurons in the central nervous system, and the formation of intracellular polyglutamine aggregates result in the loss of neurons as well as deterioration of motor functions. So far there is no effective neuroprotective treatment for this debilitating disease although numerous efforts have been made. Mesenchymal stem cells (MSCs) possess multi-lineage differentiation potentials as well as immuno-modulatory properties, and are theoretically good candidates for SCA treatment. The purpose of this study is to investigate whether transplantation of human MSCs (hMSCs) can rescue cerebellar PCs and ameliorate motor function deterioration in SCA in a pre-clinical animal model. Method Transgenic mice bearing poly-glutamine mutation in ataxin-2 gene (C57BL/6J SCA2 transgenic mice) were serially transplanted with hMSCs intravenously or intracranially before and after the onset of motor function loss. Motor function of mice was evaluated by an accelerating protocol of rotarod test every 8 weeks. Immunohistochemical stain of whole brain sections was adopted to demonstrate the neuroprotective effect of hMSC transplantation on cerebellar PCs and engraftment of hMSCs into mice brain. Results Intravenous transplantation of hMSCs effectively improved rotarod performance of SCA2 transgenic mice and delayed the onset of motor function deterioration; while intracranial transplantation failed to achieve such neuroprotective effect. Immunohistochemistry revealed that intravenous transplantation was more effective in the preservation of the survival of cerebellar PCs and engraftment of hMSCs than intracranial injection, which was compatible to rotarod performance of transplanted mice. Conclusion Intravenous transplantation of hMSCs can indeed delay the onset as well as improve the motor function of SCA2 transgenic mice. The results of this preclinical study strongly support further exploration of the feasibility to transplant hMSCs for SCA patients.

Bibliography

Chang, Y.-K., Chen, M.-H., Chiang, Y.-H., Chen, Y.-F., Ma, W.-H., Tseng, C.-Y., Soong, B.-W., Ho, J. H., & Lee, O. K. (2011). Mesenchymal stem cell transplantation ameliorates motor function deterioration of spinocerebellar ataxia by rescuing cerebellar Purkinje cells. Journal of Biomedical Science, 18(1).

Authors 9
  1. You-Kang Chang (first)
  2. Ming-Hsiang Chen (additional)
  3. Yi-Hung Chiang (additional)
  4. Yu-Fan Chen (additional)
  5. Wei-Hsien Ma (additional)
  6. Chian-You Tseng (additional)
  7. Bing-Wen Soong (additional)
  8. Jennifer H Ho (additional)
  9. Oscar K Lee (additional)
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Dates
Type When
Created 14 years ago (Aug. 9, 2011, 2:17 p.m.)
Deposited 3 years, 11 months ago (Sept. 1, 2021, 11:56 a.m.)
Indexed 11 months, 3 weeks ago (Aug. 30, 2024, 10:35 a.m.)
Issued 14 years ago (Aug. 8, 2011)
Published 14 years ago (Aug. 8, 2011)
Published Online 14 years ago (Aug. 8, 2011)
Published Print 13 years, 8 months ago (Dec. 1, 2011)
Funders 0

None

@article{Chang_2011, title={Mesenchymal stem cell transplantation ameliorates motor function deterioration of spinocerebellar ataxia by rescuing cerebellar Purkinje cells}, volume={18}, ISSN={1423-0127}, url={http://dx.doi.org/10.1186/1423-0127-18-54}, DOI={10.1186/1423-0127-18-54}, number={1}, journal={Journal of Biomedical Science}, publisher={Springer Science and Business Media LLC}, author={Chang, You-Kang and Chen, Ming-Hsiang and Chiang, Yi-Hung and Chen, Yu-Fan and Ma, Wei-Hsien and Tseng, Chian-You and Soong, Bing-Wen and Ho, Jennifer H and Lee, Oscar K}, year={2011}, month=aug }