Expression Profile of Neural, Trophic, and Immunomodulatory Genes in Multiple Sclerosis Donor-Derived Mesenchymal Stem Cell-Neural Progenitors

Jacelyn Greenwald, Saud Sadiq, MD, and Violaine Harris Presented at the Society for Neuroscience (SfN) 2019 Annual Meeting held October 19-23, 2019 in Chicago, Illinois.

Multiple sclerosis (MS) is an autoimmune-mediated demyelinating disease of the CNS. Patients with progressive MS experience a steady worsening of neurologic function attributed to chronic demyelination and axonal loss. A novel regenerative therapy utilizing autologous mesenchymal stem cell-derived neural progenitors (MSC-NP) is currently under clinical investigation in patients with progressive MS. MSC-NPs promote neural repair though the paracrine release of trophic and immuno-modulatory factors. Recent results from a phase I trial demonstrated reversal of established disability after repeated intrathecal MSC-NP injections. 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 MSC-NPs in order to better understand the mechanisms underlying therapeutic potency. The objective of this study was to define the transcriptional profile of MSC-NPs from secondary progressive MS (SPMS), primary progressive MS (PPMS), and non-MS donors in order to better understand their functional characteristics and therapeutic potential in multiple sclerosis. MSCs were derived from sternal bone marrow of MS patients (SPMS, n=4; PPMS, n=4) as part of an IRB-approved study protocol (Western IRB). MSCs from non-MS donors (n=2) 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 validated by quantitative PCR. Donor characteristics had no impact cell growth rate or the yield of MSC-NPs generated. Transcriptional profiling of MSC/MSC-NP pairs confirmed the upregulation of neural genes such as Nestin, and the downregulation of mesodermal genes such as Thy-1 and Acta2, thus affirming MSC-NP identity. In addition, gene candidates that mediate trophic/immunoregulatory mechanisms of action of MSC-NPs were identified, including HGF and TGF-ß. Characterization of the transcriptional profile of MSC-NPs has revealed potential pathways that mediate therapeutic mechanisms of this novel cell therapy in MS. These studies form the basis of marker-based potency assays that may be used to better predict the therapeutic efficacy of individual batches of autologous MSC-NPs administered to patients during clinical trials. 

Abstract Date

October 28, 2019

Abstracts archive


Tisch MS Research Center of New York

521 West 57th Street
4th Floor
New York, NY 10019
(646) 557-3900

Privacy Policy


Support Tisch MS

Support Tisch MS and our innovative research leading to treatments that improve the lives of patients.