Neuroprotective effects of human bone marrow mesenchymal stem cells against cerebral ischemia are mediated in part by an anti-apoptotic mechanism

• Published in: Neural regeneration research Vol. 14; no. 4; pp. 597 - 604
• Main Authors: Zhang, Yuyang, Yu, Seongjin, Tuazon, Julian, Lee, Jea-Young, Corey, Sydney, Kvederis, Lauren, Kingsbury, Chase, Kaneko, Yuji, Borlongan, Cesar
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer India Pvt. Ltd 01.04.2019; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd; Department of Neurosurgery and Brain Repair, Center of Excellence for Aging and Brain Repair, University of South Florida, Tampa, FL, USA; Department of Pharmacology / School of Life Science and Biopharmaceutical Science, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, China%Department of Neurosurgery and Brain Repair, Center of Excellence for Aging and Brain Repair, University of South Florida, Tampa, FL, USA; Medknow Publications & Media Pvt Ltd; Wolters Kluwer Medknow Publications
• Subjects: Apoptosis; apoptosis; Bcl-2 antibody; human mesenchymal stem cells; ischemia; neuroprotection; oxygen glucose deprivation; Bone marrow; Bone marrow cells; Care and treatment; Cellular signal transduction; Gene expression; Health aspects; Ischemia; Neurogenesis; Stem cells; Stroke; St Louis Missouri; United States > US; oxygen glucose deprivation; Bcl-2 antibody; apoptosis; human mesenchymal stem cells; neuroprotection; ischemia
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.247464

Transplantation of human bone marrow mesenchymal stem cells (hMSCs) stands as a potent stroke therapy, but its exact mechanism remains unknown. This study investigated the anti-apoptotic mechanisms by which hMSCs exert neuroprotective effects on cerebral ischemia. Primary mixed cultures of rat neurons and astrocytes were cultured and exposed to oxygen-glucose deprivation. A two-hour period of "reperfusion" in standard medium and normoxic conditions was allowed and immediately followed by hMSCs and/or Bcl-2 antibody treatment. Cell viability of primary rat neurons and astrocytes was determined by 3-(4,5-dimethylthianol-2-yl)-2,5 diphenyl tetrazolium bromide and trypan blue exclusion methods. hMSC survival and differentiation were characterized by immunocytochemistry, while the concentration of Bcl-2 in the supernatant was measured by enzyme-linked immunosorbent assay to reveal the secretory anti-apoptotic function of hMSCs. Cultured hMSCs expressed embryonic-like stem cell phenotypic markers CXCR4, Oct4, SSEA4, and Nanog, as well as immature neural phenotypic marker Nestin. Primary rat neurons and astrocytes were protected from oxygen-glucose deprivation by hMSCs, which was antagonized by the Bcl-2 antibody. However, Bcl-2 levels in the supernatants did not differ between hMSC- and non-treated cells exposed to oxygen-glucose deprivation. Neuroprotective effects of hMSCs against cerebral ischemia were partially mediated by the anti-apoptotic mechanisms. However, further studies are warranted to fully elucidate this pathway.