title: Mesenchymal stem cell transplantation ameliorates motor function deterioration of spinocerebellar ataxia by rescuing cerebellar Purkinje cells.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: You-Kang
authors.initials: YK
authors.lastname: Chang
authors.forename: Ming-Hsiang
authors.initials: MH
authors.lastname: Chen
authors.forename: Yi-Hung
authors.initials: YH
authors.lastname: Chiang
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Chen
authors.forename: Wei-Hsien
authors.initials: WH
authors.lastname: Ma
authors.forename: Chian-You
authors.initials: CY
authors.lastname: Tseng
authors.forename: Bin-Wen
authors.initials: BW
authors.lastname: Soong
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Ho
authors.forename: Oscar K
authors.initials: OK
authors.lastname: Lee
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000067528:Ataxins; D005290:Ferric Compounds; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation; D053768:Metal Nanoparticles; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D010455:Peptides / Q000235:genetics; D011689:Purkinje Cells / Q000473:pathology / Q000502:physiology*; D045442:Rotarod Performance Test; D020754:Spinocerebellar Ataxias / Q000473:pathology* / Q000628:therapy*
chemical_list: D000067528:Ataxins; D005290:Ferric Compounds; D009419:Nerve Tissue Proteins; D010455:Peptides; C000499:ferric oxide; C097188:polyglutamine