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).