Protective function of adipocyte-derived extracellular vesicles and adipose stem cells in damage repair and regeneration

Abstract

Adipocyte-secreted extracellular vesicles (EVs) and adipose-derived stem cells (ADSCs) regulate physiological and pathological processes by delivering nucleic acids, proteins, and lipids. Both adipocyte- and ADSC-derived EVs regulate local inflammatory levels, tumor progression, and insulin sensitivity. These two types of EVs also have significant therapeutic effects on damage repair, including wound healing, angiogenesis, myocardial damage, vessel re-endothelialization, bone and cartilage regeneration, muscle repair, and nerve repair. With regard to wound healing, microRNA-21, microRNA-126, microRNA-31, and long non-coding RNA-H19 accelerate the proliferation and migration of fibroblasts, human immortalized keratinocytes, and endothelial cells via the PI3K/Akt/ERK pathway or fibrillin 1. ADSC-derived EVs contain various growth factors that are beneficial for wound healing. Numerous miRNAs in ADSC-derived EVs and β3-adrenergic receptors on brown adipocytes exhibit protective effects against myocardial infarction. Proteins in adipocyte- and ADSC-derived EVs play a role in promoting vessel re-endothelialization and regulating vasodilation. Angiogenesis is beneficial for the regeneration and repair of injured bone, cartilage, muscle, and nerves. Compared with adipocyte EVs, ADSC-EVs contain a greater variety of miRNAs and proteins that promote tissue regeneration. EV therapy is a promising cell-free therapy, and EV-loaded materials have been used for wound healing and myocardial damage. Future research will focus on identifying the molecules in EVs and the repair mechanisms that contribute to damage repair and regeneration. In addition, we aim to discover materials designed for slow release and specificity to facilitate tissue repair and optimize EV transportation.