Recent advances in the use of extracellular vesicles from adipose-derived stem cells for regenerative medical therapeutics

Abstract

Adipose-derived stem cells (ADSCs) are a subset of mesenchymal stem cells (MSCs) isolated from adipose tissue. They possess remarkable properties, including multipotency, self-renewal, and easy clinical availability. ADSCs are also capable of promoting tissue regeneration through the secretion of various cytokines, factors, and extracellular vesicles (EVs). ADSC-derived EVs (ADSC-EVs) act as intercellular signaling mediators that encapsulate a range of biomolecules. These EVs have been found to mediate the therapeutic activities of donor cells by promoting the proliferation and migration of effector cells, facilitating angiogenesis, modulating immunity, and performing other specific functions in different tissues. Compared to the donor cells themselves, ADSC-EVs offer advantages such as fewer safety concerns and more convenient transportation and storage for clinical application. As a result, these EVs have received significant attention as cell-free therapeutic agents with potential future application in regenerative medicine. In this review, we focus on recent research progress regarding regenerative medical use of ADSC-EVs across various medical conditions, including wound healing, chronic limb ischemia, angiogenesis, myocardial infarction, diabetic nephropathy, fat graft survival, bone regeneration, cartilage regeneration, tendinopathy and tendon healing, peripheral nerve regeneration, and acute lung injury, among others. We also discuss the underlying mechanisms responsible for inducing these therapeutic effects. We believe that deciphering the biological properties, therapeutic effects, and underlying mechanisms associated with ADSC-EVs will provide a foundation for developing a novel therapeutic approach in regenerative medicine.

Keywords: Adipose-derived stem cell; Extracellular vesicle; Regenerative medicine; Therapeutic effect; Tissue regeneration; Underlying mechanism.

Fig. 1

Cellular biogenesis and uptake of EVs. The EV biogenesis pathways include the outward budding of plasma membrane domains to form ectosomes, and the development of endosomes to release exosomes. The EV uptake pathways include entry of intact EVs through endocytosis, direct ligand-receptor binding triggered intracellular signaling without internalization or releasing the contents, and the release of EV contents inward via direct membrane fusion

Fig. 2

Preparation of ADSC-EVs, the four sequential phases of wound healing, and ADSC-EV-induced promotion of wound healing. ADSC-EVs promote wound healing by enhancing cell proliferation and migration, stimulating angiogenesis, facilitating myofibroblast infiltration, promoting collagen production and deposition, accelerating re-epithelialization and tissue layer growth, as well as suppressing inflammation when it is time to move on to the next phase. Created with MedPeer (medpeer.cn)

Fig. 3

Regenerative medical conditions that are affected by ADSC-EVs and the major mechanisms of tissue regenerative efficacy. The recent advances in the regenerative medical use of ADSC-EVs focus mainly on these listed conditions. And, the most common primary mechanisms of tissue regenerative effects involve stimulated cell proliferation, migration and angiogenesis, and suppressed inflammation. Created with MedPeer (medpeer.cn)