Gap junction‐mediated cell‐cell interaction between transplanted mesenchymal stem cells and vascular endothelium in stroke. (11th March 2021)

• Record Type: Journal Article
• Authors: Kikuchi‐Taura, Akie; Okinaka, Yuka; Saino, Orie; Takeuchi, Yukiko; Ogawa, Yuko; Kimura, Takafumi; Gul, Sheraz; Claussen, Carsten; Boltze, Johannes; Taguchi, Akihiko
• Is Part Of: Stem cells. Volume 39:Number 7(2021)
• Page Start: 904
• Page End: 912
• Publication Date: 2021-03-11
• Subjects: cell therapy -- COVID‐19 -- gap junction -- immunosuppression -- mesenchymal stem cell; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.3360
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: We have shown previously that transplanted bone marrow mononuclear cells (BM‐MNC), which are a cell fraction rich in hematopoietic stem cells, can activate cerebral endothelial cells via gap junction‐mediated cell‐cell interaction. In the present study, we investigated such cell‐cell interaction between mesenchymal stem cells (MSC) and cerebral endothelial cells. In contrast to BM‐MNC, for MSC we observed suppression of vascular endothelial growth factor uptake into endothelial cells and transfer of glucose from endothelial cells to MSC in vitro . The transfer of such a small molecule from MSC to vascular endothelium was subsequently confirmed in vivo and was followed by suppressed activation of macrophage/microglia in stroke mice. The suppressive effect was absent by blockade of gap junction at MSC. Furthermore, gap junction‐mediated cell‐cell interaction was observed between circulating white blood cells and MSC. Our findings indicate that gap junction‐mediated cell‐cell interaction is one of the major pathways for MSC‐mediated suppression of inflammation in the brain following stroke and provides a novel strategy to maintain the blood‐brain barrier in injured brain. Furthermore, our current results have the potential to provide a novel insight for other ongoing clinical trials that make use of MSC transplantation aiming to suppress excess inflammation, as well as other diseases such as COVID‐19 (coronavirus disease 2019). Abstract : Ten minutes after BCECF‐loaded mesenchymal stem cells transplantation, the expression of connexin 37 were observed in the cell membrane of endothelial cells which are adjacent to the transferred BCECF signal at nuclei/cytosol of the cells.