Mitochondrial Transfer to Endothelial Cells: Mechanisms, Evidence, and Therapeutic Potential.

Abstract

Mitochondria are increasingly recognized as central regulators of vascular health, shaping endothelial cell function through roles that extend far beyond energy production. In addition to coordinating redox balance, calcium dynamics, and biosynthetic support, recent studies have revealed that mitochondria participate in intercellular communication, with evidence of transfer events emerging in vascular contexts. Parallel efforts have advanced the deliberate delivery of exogenous mitochondria from preclinical proof-of-principle studies to first-in-human trials, demonstrating that freshly isolated organelles can be harvested and administered in real-time to critically ill patients with favorable early outcomes. The mechanisms underlying these benefits remain incompletely defined, and strategies for efficient and scalable delivery are still emerging. In this review, we prioritize recent evidence linking mitochondrial function to endothelial cell physiology, highlight the nascent but growing field of mitochondrial transfer in the vasculature, and examine how mitochondrial transplantation is evolving from experimental concept to clinical translation. Together, these advances point to new therapeutic avenues for preserving vascular integrity and treating disease.