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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, FÂé¶¹´«Ã½Ó³»­ (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