Mesenchymal stem cell-neural progenitors are enriched in cell signaling molecules implicated in their therapeutic effect in multiple sclerosis.

Mesenchymal stem cell-neural progenitors (MSC-NP) are a neural derivative of MSCs that are being investigated in clinical trials as an autologous intrathecal cell therapy to treat patients with secondary progressive (SP) or primary progressive (PP) multiple sclerosis (MS). MSC-NPs promote tissue repair through paracrine mechanisms, however which secreted factors mediate the therapeutic potential of MSC-NPs and how this cell population differs from MSCs remain poorly understood. The objective of this study was to define the transcriptional profile of MSCs and MSC-NPs from MS and non-MS donors to better characterize each cell population. MSCs derived from SPMS, PPMS, or non-MS bone marrow donors demonstrated minimal differential gene expression, despite differences in disease status. MSC-NPs from both MS and non-MS-donors exhibited significant differential gene expression compared to MSCs, with 2,156 and 1,467 genes upregulated and downregulated, respectively. Gene ontology analysis demonstrated pronounced downregulation of cell cycle genes in MSC-NPs compared to MSC consistent with reduced proliferation of MSC-NPs in vitro. In addition, MSC-NPs demonstrated significant enrichment of genes involved in cell signaling, cell communication, neuronal differentiation, chemotaxis, migration, and complement activation. These findings suggest that increased cell signaling and chemotactic capability of MSC-NPs may support their therapeutic potential in MS.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Authors Violaine Harris and Saud Sadiq are listed as inventors on US patent #US 8,642,331, which is related to the study presented in the manuscript. The patent is issued to the Tisch MS Research Center of New York and is considered a non-financial competing interest. This does not alter our adherence to PLOS ONE policies on sharing data or materials. Furthermore, Violaine Harris and Saud Sadiq have no other relevant declarations related to employment, consultancy, products in development, etc. The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright: © 2023 Harris et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)