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

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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.

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Acknowledgment

The authors thank Moshe Mizrachy, Alejandro Aran, and Debi Iskovich for their technical assistance. The work was performed in partial fulfillment of the requirements for a Ph.D. degree of Merav Bahat-Stromza, Sackler Faculty of Medicine, Tel Aviv University, Israel. The study was partially supported by The National Parkinson Foundation, USA, The Norma and Alan Aufzien Chair for Research in Parkinson’s Disease, Tel Aviv University, Israel (E.M.), Brainstorm Cell Therapeutics Ltd, and the Ted Arison Family Foundation.

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Authors and Affiliations

  1. Laboratory of Neurosciences, Felsenstein Medical Research, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Merav Bahat-Stroomza, Yael Barhum, Yossef S. Levy, Eldad Melamed & Daniel Offen

  2. Department of Neurology, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel

    Merav Bahat-Stroomza, Yael Barhum, Yossef S. Levy, Eldad Melamed & Daniel Offen

  3. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Merav Bahat-Stroomza, Yael Barhum, Yossef S. Levy, Eldad Melamed & Daniel Offen

  4. Laniado Medical Center, Netanya, Israel

    Shlomo Bulvik

  5. Brainstorm Cell Therapeutics Ltd, 12 Bazel St., Kiryat Arie, Petach Tikva, Israel

    Olga Karpov

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  1. Merav Bahat-Stroomza
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  2. Yael Barhum
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  3. Yossef S. Levy
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  4. Olga Karpov
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  6. Eldad Melamed
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  7. Daniel Offen
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Correspondence to Daniel Offen.

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Bahat-Stroomza, M., Barhum, Y., Levy, Y.S. et al. Induction of Adult Human Bone Marrow Mesenchymal Stromal Cells into Functional Astrocyte-Like Cells: Potential for Restorative Treatment in Parkinson’s Disease. J Mol Neurosci 39, 199–210 (2009). https://doi.org/10.1007/s12031-008-9166-3

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