Mesenchymal stem cells transplanted into spinal cord injury adopt immune cell-like characteristics

Abstract

Background Mesenchymal stem cells (MSCs) and their cellular response to various stimuli have been characterized in great detail in culture conditions. In contrast, the cellular response of MSCs in an in vivo setting is still uncharted territory. In this study, we investigated the cellular response of MSCs following transplantation into spinal cord injury (SCI). Methods Mouse bone marrow-derived MSCs were transplanted 24 h following severe contusion SCI in mice. As controls, MSCs transplanted to the uninjured spinal cord and non-transplanted MSCs were used. At 7 days post transplantation, the MSCs were isolated from the SCI, and their global transcriptional changes, survival, differentiation, proliferation, apoptosis, and phenotypes were investigated using RNA sequencing, immunohistochemistry, and flow cytometry. Results MSCs transplanted into SCI downregulated genes related to cell-cycle regulation/progression, DNA metabolic/biosynthetic process, and DNA repair and upregulated genes related to immune system response, cytokine production/response, response to stress/stimuli, signal transduction and signaling pathways, apoptosis, and phagocytosis/endocytosis. MSCs maintained their surface expression of Sca1 and CD29 but upregulated expression of CD45 following transplantation. Transplanted MSCs maintained their surface expression of MHC-I but upregulated surface expression of MHC-II. Transplanted MSCs survived and proliferated to a low extent, did not express Caspase-3, and did not differentiate into neurons or astrocytes. Conclusion MSCs transplanted into SCI upregulate expression of CD45 and MHC-II and expression of genes related to cytokine production, phagocytosis/endocytosis, and immune cells/response and thereby adopt immune cell-like characteristics within the recipient. Electronic supplementary material The online version of this article (10.1186/s13287-019-1218-9) contains supplementary material, which is available to authorized users.

SDF-1/CXCR4 Axis-mediated Migration of Systematically Transplanted Bone Marrow Mesenchymal Stem Cells Towards the Injured Spinal Cord in a Rat Model

“…It is known that the adult CNS, especially the injured CNS, may provide a relatively non-permissive environment for transplanted MSCs and other stem cells [43,53,54]. Even under the best circumstances, cell survival in injured CNS has been estimated to be less than 10% [43,55,56].…”

“…5). One of the most important reasons why those cells could not survive in the injured spinal cord for a long time is probably due to the sustained in ammation in the injury sites or the immediate in ammatory response elicited by surgery and injection manipulation [53,56,57].…”

Mesenchymal stromal cells as a choice for spinal cord injury treatment

“…Although most studies showed evidence that MSCs most likely act through their secretions (paracrine effect) [46][47][48] and not via their own integration/differentiation within the host tissue, some authors have reported the potential for MSCs transdifferentiation in cells of the nervous system and have shown that, after infusion into the spinal cord, these cells possibly promote regeneration of neurons because they have neuronal markers [49][50][51][52] . In vitro studies have shown that BM-MSC possess an intrinsic capacity to differentiate into neural-like and glial-like cells and express nestin, βIII-tubulin, neurofilaments, neuronspecific enolase, and glial fibrillary acidic protein (GFAP) [53][54][55] .…”

Comparisons of neurotrophic effects of mesenchymal stem cells derived from adipose tissue, bone marrow, and cranial bone on chronic spinal cord injury

“…Thus, unique characteristics of MSCs derived from various tissues may have different therapeutic effects due to their unique characteristics. Although it is necessary to choose optimal MSCs for each central nervous system (CNS) disease and stage of illness, the timing of treatment with MSCs for SCI was mainly in the acute or subacute phase in previous studies [25][26][27]. In addition, relatively few reports have investigated differences in the therapeutic effects of MSCs derived from various tissued on chronic SCI.…”