Journal of Molecular Neuroscience

, Volume 39, Issue 1, pp 199–210

Induction of Adult Human Bone Marrow Mesenchymal Stromal Cells into Functional Astrocyte-Like Cells: Potential for Restorative Treatment in Parkinson’s Disease

  • Merav Bahat-Stroomza
  • Yael Barhum
  • Yossef S. Levy
  • Olga Karpov
  • Shlomo Bulvik
  • Eldad Melamed
  • Daniel Offen
Article

DOI: 10.1007/s12031-008-9166-3

Cite this article as:
Bahat-Stroomza, M., Barhum, Y., Levy, Y.S. et al. J Mol Neurosci (2009) 39: 199. doi:10.1007/s12031-008-9166-3

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder with its motor phenomena due mostly to loss of dopamine-producing neurons in the substantia nigra. Pharmacological treatments aimed to increase the deficient dopaminergic neurotransmission are effective in ameliorating the cardinal symptoms, but none of these therapies is curative. It has been suggested that treatment with neurotrophic factors (NTFs) might protect and prevent death of the surviving dopaminergic neurons and induce proliferation of their axonal nerve terminals with reinnervations of the deafferented striatum. However, long-term delivery of such proteins into the CNS is problematic. We therefore aimed to differentiate ex vivo human bone marrow-derived mesenchymal stromal cells into astrocyte-like cells, capable of generating NTFs for future transplantation into basal ganglia of PD patients. Indeed, mesenchymal stromal cells treated with our novel astrocyte differentiation medium, present astrocyte-like morphology and express the astrocyte markers S100β, glutamine synthetase and glial fibrillary acidic protein. Moreover, these astrocyte-like cells produce and secrete significant amounts of glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and brain-derived neurotrophic factor as indicated by messenger RNA, real-time polymerase chain reaction, ELISA, and Western blot analyses. Such NTF-producing cells transplanted into the striatum of 6-hydroxydopamine-lesioned rats, a model of PD, produced a progressive reduction in the apomorphine-induced contralateral rotations as well as behavioral improvement in rotor-rod and the “sunflower seeds” eating motor tests. Histological assessments revealed that the engrafted cells survived and expressed astrocyte and human markers and acted to regenerate the damaged dopaminergic nerve terminal system. Findings indicate that our novel procedure to induce NTF-producing astrocyte-like cells derived from human bone marrow stromal cells might become a promising and feasible autologous transplantation strategy for PD.

Keywords

Mesenchymal stromal cells 6-Hydroxydopamine Astrocytes Parkinson’s disease Neurotrophic factors 

Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  • Merav Bahat-Stroomza
    • 1
    • 2
    • 3
  • Yael Barhum
    • 1
    • 2
    • 3
  • Yossef S. Levy
    • 1
    • 2
    • 3
  • Olga Karpov
    • 5
  • Shlomo Bulvik
    • 4
  • Eldad Melamed
    • 1
    • 2
    • 3
  • Daniel Offen
    • 1
    • 2
    • 3
  1. 1.Laboratory of Neurosciences, Felsenstein Medical ResearchSackler Faculty of Medicine, Tel Aviv UniversityTel AvivIsrael
  2. 2.Department of NeurologyRabin Medical CenterPetach TikvaIsrael
  3. 3.Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
  4. 4.Laniado Medical CenterNetanyaIsrael
  5. 5.Brainstorm Cell Therapeutics LtdPetach TikvaIsrael

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