Mitochondrial transfer mediates endothelial cell engraftment through mitophagy.
Ruei-Zeng LinGwang-Bum ImAllen Chilun LuoYonglin ZhuXuechong HongJoseph NeumeyerHong-Wen TangNorbert PerrimonJuan M Melero-MartinPublished in: Nature (2024)
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.
Keyphrases
- endothelial cells
- mesenchymal stem cells
- cell therapy
- umbilical cord
- cell death
- bone marrow
- oxidative stress
- endoplasmic reticulum
- reactive oxygen species
- hematopoietic stem cell
- stem cells
- high glucose
- cell cycle arrest
- induced apoptosis
- healthcare
- primary care
- heart failure
- vascular endothelial growth factor
- gene expression
- signaling pathway
- genome wide
- cell proliferation
- risk assessment
- quality improvement
- endoplasmic reticulum stress
- climate change
- radiofrequency ablation