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Abstract Details

Transcriptional Profiling of Autologous Bone Marrow Mesenchymal Stem Cell-Derived Neural Progenitors (MSC-NPs) from Patients with Multiple Sclerosis
Multiple Sclerosis
P2 - Poster Session 2 (5:30 PM-6:30 PM)
15-090

To define the transcriptional profile of MSC-NPs from MS and non-MS donors in order to better understand their functional characteristics and therapeutic potential in multiple sclerosis. 

Repeated intrathecal administration of autologous bone marrow mesenchymal stem cell-derived neural progenitors (MSC-NP) is currently under clinical investigation as a cell-based strategy to promote neural repair in patients with progressive MS. An initial phase I trial in 20 patients demonstrated safety and tolerability of the treatment, and a phase II randomized double-blind placebo-controlled trial is underway to confirm the efficacy of this approach. As this autologous cell therapy moves into clinical use, there is a need to better define and characterize the MSC-NPs in order to better understand the mechanisms underlying therapeutic potency.

MSCs were derived from sternal bone marrow of MS patients as part of an IRB-approved study protocol (Western IRB). MSCs from non-MS donors were isolated from commercially available bone marrow aspirates. MSCs were expanded for up to 4 passages in growth medium containing 5% human platelet lysate, then transferred to neural progenitor medium containing EGF/bFGF to generate MSC-

NPs. Population doubling time (PDT) of MSCs was determined by cell counting. RNA isolated from MSC and MSC-NP cells was analyzed for gene expression differences by RNA sequencing and by TaqMan® gene expression assay.

To determine whether donor characteristics influence the growth of MSCs, we measured the PDT of MS-derived MSCs (n=47) compared to non-MS controls (n=5). We found no correlation between PDT and disease duration, donor age, or disease subtype. Furthermore, donor characteristics had no impact on the yield of MSC-NPs generated. Transcriptional profiling of MSC/MSC-NP pairs demonstrated upregulation of gene candidates that mediate trophic/immunoregulatory mechanisms of action of MSC-NPs.

Characterization of the transcriptional profile of MSC-NPs has revealed potential pathways that mediate therapeutic mechanisms of this novel cell therapy in MS.

 

Authors/Disclosures

PRESENTER
No disclosure on file
Tamara Vyshkina, PhD (Tisch Multiple Sclerosis Research Ctr of NY) No disclosure on file
Saud Sadiq, BS, FAAN (Tisch Multiple Sclerosis Research Center of New York) Ms. Brewi has nothing to disclose.
Violaine K. Harris, PhD (Tisch Multiple Sclerosis Research Center of NY) No disclosure on file