The Use of Bone Marrow Derived Mesenchymal Stromal Cells for Treatment of Patients with Multiple Sclerosis and Neurodegenerative Disorders – Achievements and Future Goals

S. Slavin, C. Brodie

Research output: Contribution to journalArticlepeer-review

Abstract

Future treatment of multiple sclerosis (MS) aims at restoring myelination and neurological functions as well as re-induction of self-tolerance. We studied the role of mesenchymal stromal stem cells (MSC), known to be anti-inflammatory on the one hand and multi-potent on the other, in experimental autoimmune encephalitis (EAE), and found that treatment of mice with bone marrow derived MSCs resulted in significant suppression of anti-self reactivity and improved clinical and pathological disease manifestations. Using green fluorescent donors, we documented that in addition to down regulation of autoimmunity, neural differentiation of these cells may occur in vivo. These observations suggested that treatment with MSCs might be used for immune regulation and neuroprotection for patients with MS. Our preliminary results of a phase I/II open clinical trial to evaluate the feasibility and safety of intrathecal and intravenous administration of autologous bone marrow derived MSCs in patients with severe MS failing conventional modalities suggested that treatment with MSCs is feasible, safe and potentially effective. No major side effect were developed or reported during a follow up period of nearly 4 years. Based on our successful preliminary pilot study in 13 patients with MS and 14 with ALS, a total of >150 patients were treated with autologous bone marrow derived MSCs, mostly >100 patients with MS alone were treated at our center with MSCs administered partially intrathecally (106 MSC/Kg) and additional 5 - 10x105/Kg intravenously. The treatment was uneventful with headache due to lumbar puncture being the most frequent complaint (70%) and self-limited subfebrile temperature in 25% and no serious side effect. A total of 60 % of patients reported improved outcome, in some with very significant objective improvement of disease manifestations with subjective and objective improvement of EDSS score. More recently, we have discovered a new proprietary technology which allows differentiation of both bone marrow, adipose tissue derived and cord/placenta derived MSCs into neural stem cells, motor neurons, dopaminergic neurons, astrocytes and myelin basic protein secreting oligodendrocytes that in principle may be used to induce remyelination. These results suggest that treatment with MSCs may provide the most suitable approach for treatment of MS, which could also be applicable for treatment of other neurodegenerative disorders.
Original languageEnglish
Article number145
Pages (from-to)S257-S258
JournalBiology of Blood and Marrow Transplantation
Volume18
Issue number2, Supplement
DOIs
StatePublished - Feb 2012

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