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

Stem Cell Research & Therapy

Sreenivasa Raghavan Sankavaram¹  Arvid Frostell²  Mikael Svensson²  Lou Brundin³  Ramil Hakim³  Ruxandra Covacu³  Vasilios Zachariadis⁴ 

[1] Center for Molecular Medicine, Karolinska Institutet;Department of Clinical Neuroscience, Karolinska Institutet;Department of Neurology, Karolinska University Hospital;Department of Oncology and Pathology, Karolinska Institutet;

关键词: Mesenchymal stem cells;    Spinal cord injury;    Cellular response;    Transcriptional changes;    Phenotypes;    Differentiation;   

DOI  :  10.1186/s13287-019-1218-9

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown