Gap junction-mediated cell-cell interaction between transplanted mesenchymal stem cells and vascular endothelium in stroke.

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Abstrakt

Tytuł:: Gap junction-mediated cell-cell interaction between transplanted mesenchymal stem cells and vascular endothelium in stroke.
Autorzy:: Kikuchi-Taura A; Department of Regenerative Medicine Research, Foundation for Biomedical Research and Innovation at Kobe, Hyogo, Japan.
Okinaka Y; Department of Regenerative Medicine Research, Foundation for Biomedical Research and Innovation at Kobe, Hyogo, Japan.
Saino O; Department of Regenerative Medicine Research, Foundation for Biomedical Research and Innovation at Kobe, Hyogo, Japan.
Takeuchi Y; Department of Regenerative Medicine Research, Foundation for Biomedical Research and Innovation at Kobe, Hyogo, Japan.
Ogawa Y; Department of Regenerative Medicine Research, Foundation for Biomedical Research and Innovation at Kobe, Hyogo, Japan.
Kimura T; Japanese Red Cross Kinki Block Blood Center, Osaka, Japan.
Gul S; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Hamburg, Germany.; Fraunhofer Cluster of Excellence for Immune-Mediated Diseases CIMD, Hamburg, Germany.
Claussen C; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Hamburg, Germany.; Fraunhofer Cluster of Excellence for Immune-Mediated Diseases CIMD, Hamburg, Germany.
Boltze J; Department of Regenerative Medicine Research, Foundation for Biomedical Research and Innovation at Kobe, Hyogo, Japan.; School of Life Sciences, University of Warwick, Coventry, UK.
Taguchi A; Department of Regenerative Medicine Research, Foundation for Biomedical Research and Innovation at Kobe, Hyogo, Japan.
Źródło:: Stem cells (Dayton, Ohio) [Stem Cells] 2021 Jul; Vol. 39 (7), pp. 904-912. Date of Electronic Publication: 2021 Mar 11.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: 2022- : Oxford : Oxford University Press
Original Publication: Dayton, OH : AlphaMed Press, c1993-
MeSH Terms:: Cell Communication*
Gap Junctions*/metabolism
Gap Junctions*/pathology
Mesenchymal Stem Cell Transplantation*
Mesenchymal Stem Cells*/metabolism
Mesenchymal Stem Cells*/pathology
Stroke*/metabolism
Stroke*/pathology
Stroke*/therapy
Human Umbilical Vein Endothelial Cells/*metabolism
Allografts ; Animals ; COVID-19/metabolism ; COVID-19/pathology ; Human Umbilical Vein Endothelial Cells/pathology ; Humans ; Mice ; SARS-CoV-2/metabolism
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Grant Information:: A79 Japan Agency for Medical Research and Development
Contributed Indexing:: Keywords: COVID-19; cell therapy; gap junction; immunosuppression; mesenchymal stem cell
Entry Date(s):: Date Created: 20210311 Date Completed: 20210705 Latest Revision: 20240405
Update Code:: 20240405
PubMed Central ID:: PMC8807299
DOI:: 10.1002/stem.3360
PMID:: 33704866
: Czasopismo naukowe

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).
(©AlphaMed Press 2021.)

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