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Mitochondrial transfer mediates endothelial cell engraftment through mitophagy
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Journal Article
Mitochondrial transfer mediates endothelial cell engraftment through mitophagy
2024
Overview
Ischaemic diseases such as critical limb ischaemia and myocardial infarction affect millions of people worldwide
1
. Transplanting endothelial cells (ECs) is a promising therapy in vascular medicine, but engrafting ECs typically necessitates co-transplanting perivascular supporting cells such as mesenchymal stromal cells (MSCs), which makes clinical implementation complicated
2
,
3
. The mechanisms that enable MSCs to facilitate EC engraftment remain elusive. Here we show that, under cellular stress, MSCs transfer mitochondria to ECs through tunnelling nanotubes, and that blocking this transfer impairs EC engraftment. We devised a strategy to artificially transplant mitochondria, transiently enhancing EC bioenergetics and enabling them to form functional vessels in ischaemic tissues without the support of MSCs. Notably, exogenous mitochondria did not integrate into the endogenous EC mitochondrial pool, but triggered mitophagy after internalization. Transplanted mitochondria co-localized with autophagosomes, and ablation of the PINK1–Parkin pathway negated the enhanced engraftment ability of ECs. Our findings reveal a mechanism that underlies the effects of mitochondrial transfer between mesenchymal and endothelial cells, and offer potential for a new approach for vascular cell therapy.
Under stressful conditions, mesenchymal stromal cells transfer mitochondria to endothelial cells through tunnelling nanotubes, and artificially transplanting mitochondria into endothelial cells improves the ability of these cells to engraft and to revascularize ischaemic tissues.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 14
/ 38
/ 59
/ Ablation
/ Animals
/ Cell- and Tissue-Based Therapy - methods
/ Endothelial Cells - cytology
/ Endothelial Cells - metabolism
/ Endothelial Cells - transplantation
/ Human Umbilical Vein Endothelial Cells - metabolism
/ Humanities and Social Sciences
/ Humans
/ Ischemia
/ Male
/ Mesenchymal Stem Cells - cytology
/ Mesenchymal Stem Cells - metabolism
/ Mice
/ Mitochondria - transplantation
/ Protein Kinases - deficiency
/ Protein Kinases - metabolism
/ Science
