Journal
STEM CELLS
Volume 39, Issue 7, Pages 904-912Publisher
WILEY
DOI: 10.1002/stem.3360
Keywords
cell therapy; COVID-19; gap junction; immunosuppression; mesenchymal stem cell
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Funding
- Japan Agency for Medical Research and Development [A79]
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The study revealed that mesenchymal stem cells can suppress inflammation in the brain through cell-cell interaction, potentially offering a new strategy to maintain the blood-brain barrier in injured brain. This finding may provide new insights for clinical trials using MSC transplantation to suppress excess inflammation, including in diseases like COVID-19.
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).
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