Intravenous mesenchymal stem cell administration exhibits therapeutic effects against 6-hydroxydopamine-induced dopaminergic neurodegeneration and glial activation in rats

Neurosci Lett. 2015 Jan 1:584:276-81. doi: 10.1016/j.neulet.2014.10.039. Epub 2014 Nov 1.

Abstract

To explore a novel therapy against Parkinson's disease (PD), we evaluated the therapeutic effects of human bone marrow-derived mesenchymal stem cells (hBM-MSCs), pluripotent stromal cells with secretory potential of various neurotrophic and anti-inflammatory factors, in a hemi-parkinsonian rat model. The unilateral intrastriatal 6-hydroxydopamine (6-OHDA)-lesioned rats were injected hBM-MSCs (1.0 × 10(7)cells) or PBS intravenously 16 days after lesioning. Administration of hBM-MSCs inhibited methamphetamine-stimulated rotational behavior at 7, 14, 21 and 28 days after transplantation. Immunohistochemical analysis also showed that number of TH-positive neurons in the substantia nigra pars compacta was significantly preserved in hBM-MSCs-transplanted rats compared to sham-operated rats, whereas the immunoreactivity of ionized calcium binding adaptor molecule 1 was markedly inhibited. In this study, we demonstrated the therapeutic effects of intravenous hBM-MSCs administration in parkinsonian model rats presenting distinct parkinsonian phenotype at 16 days after 6-OHDA lesioning. The favorable findings raise the possibility that hBM-MSCs could be a novel therapeutic option to promote survival of dopaminergic neurons in PD.

Keywords: 6-Hydroxydopamine; Anti-inflammatory; Mesenchymal stem cell; Neuroprotection; Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopaminergic Neurons / pathology*
  • Female
  • Humans
  • Mesenchymal Stem Cell Transplantation*
  • Methamphetamine / pharmacology
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / pathology
  • Nerve Degeneration / therapy
  • Neuroglia / metabolism*
  • Oxidopamine
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / pathology
  • Parkinsonian Disorders / therapy*
  • Rats, Sprague-Dawley
  • Stereotyped Behavior / drug effects
  • Substantia Nigra / metabolism
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Methamphetamine
  • Oxidopamine
  • Tyrosine 3-Monooxygenase