Mesenchymal stromal SB623 cell implantation mitigates nigrostriatal dopaminergic damage in a mouse model of Parkinson's disease

J Tissue Eng Regen Med. 2017 Jun;11(6):1835-1843. doi: 10.1002/term.2081. Epub 2015 Oct 6.

Abstract

Regenerative medicine for the treatment of motor features in Parkinson's disease (PD) is a promising therapeutic option. Donor cells can simultaneously address multiple pathological mechanisms while responding to the needs of the host tissue. Previous studies have demonstrated that mesenchymal stromal cells (MSCs) promote recovery using various animal models of PD. SanBio Inc. has developed a novel cell type designated SB623, which are adult bone marrow-derived MSCs transfected with Notch intracellular domain. In this preclinical study, SB623 cells protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced nigrostriatal injury when transplanted unilaterally into C57BL/6 mouse striatum 3 days prior to toxin exposure. Specifically, mice with the SB623 cell transplants revealed significantly higher levels of striatal dopamine, tyrosine hydroxylase immunoreactivity and stereological nigral cell counts in the ipsilateral hemisphere vs vehicle-treated mice following MPTP administration. Interestingly, improvement in markers of striatal dopaminergic integrity was also noted in the contralateral hemisphere. These data indicate that MSCs transplantation, specifically SB623 cells, may represent a novel therapeutic option to ameliorate damage related to PD, not only at the level of striatal terminals (i.e. the site of implantation) but also at the level of the nigral cell body. Copyright © 2015 John Wiley & Sons, Ltd.

Keywords: MPTP; Parkinson's disease; dopamine; mesenchymal stromal cells; mouse; neuroprotection; nigrostriatal.

MeSH terms

  • Adult
  • Animals
  • Cells, Cultured
  • Corpus Striatum* / metabolism
  • Corpus Striatum* / pathology
  • Disease Models, Animal
  • Dopamine / metabolism*
  • Female
  • Heterografts
  • Humans
  • MPTP Poisoning* / metabolism
  • MPTP Poisoning* / pathology
  • MPTP Poisoning* / therapy
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / metabolism*
  • Mesenchymal Stem Cells / pathology
  • Mice

Substances

  • Dopamine