Mitochondrial Transfer/Transplant in Skin: Reducing ROS Damage, Enhancing Proliferation and Wound Healing

Abstract

Abstract The intricate cellular composition of the skin encompasses dynamic interactions among melanocytes, keratinocytes, and fibroblasts, crucial for protective responses to ultraviolet radiation (UVR), wound healing and aging. Recent insights underline mitochondrial transfer as pivotal in cellular repair, yet its occurrence between skin cells remains unclear. Our research probes mitochondrial exchanges between skin cells, especially post-UVR exposure, uncovering a predominance of transfer via tunneling nanotubes (TNTs) over microvesicles (MVs). Notably, fibroblasts show diminished mitochondrial acquisition, possibly accelerating aging and reactive oxygen species (ROS)-induced damage. To counteract this, we subjected fibroblasts to UVR, augmenting ROS production, and then initiated Artificial Mitochondrial Transfer/Transplant (AMT/T) using Mesenchymal stem cells (MSCs) as a source. This intervention markedly boosted fibroblast proliferation, countering the adverse effects of UVR-related stress reflected in reduced proliferation and escalated ROS levels. Investigating AMT/T's therapeutic potential, we applied MSC-sourced mitochondria to a mouse surgical wound model, resulting in a faster wound healing with minimal mitochondria (25 ng) and MSCs (250,000) introduced. These results emphasize mitochondrial transfer's critical role in skin cellular defense mechanisms, presenting a novel strategy for mitigating UVR-induced damage, enhancing wound recovery, and the potential shielding of skin from environmental stressors.