Mesenchymal Stem Cell Derived Extracellular Vesicles: Promising Nanomedicine for Cutaneous Wound Treatment

A skin wound represents a rupture caused by external damage or the existence of underlying pathological conditions. Sometimes, skin wound healing processes may place a heavy burden on patients, families, and society. Wound healing processes mainly consist of several continuous, dynamic, but overlapping stages, namely, the coagulation stage, inflammation stage, proliferation stage, and remodeling stage. Bacterial infection, excessive inflammation, impaired angiogenesis, and scar formation constitute the four significant factors impeding the recovery efficacy of skin wounds. This encourages scientists to develop multifunctional nanomedicines to meet challenging needs. As we know, mesenchymal stem cells (MSCs) have been widely explored for wound repair owing to their unique capability for self-renewal and multipotency. However, problems including immune concerns and legal restrictions should be properly resolved before MSC-based therapeutics are safely and widely used in clinics. Besides, maintaining the high viability/ proliferation capability of MSCs during administration processes and therapy procedures is also one of the biggest technical bottlenecks. Extracellular vesicles (EVs) are cell-derived nanovesicles, that not only possess the basic characteristics and functions of their corresponding maternal cells but also contain several outstanding advantages including abundant sources, excellent biocompatibility, and convenient administration routes. Furthermore, the membrane surface and cavity are easy to flexibly modify to meet versatile application needs. Recently, MSC-derived EVs have emerged as promising therapeutics for skin wound repair. However, current reviews are too broad and rarely focused on the specific roles of EVs in the different stages of wound recovery. Therefore, it is quite necessary to demonstrate the significance of stem cell-derived EVs in promoting wound healing from several specific aspects. Here, this review primarily tries to provide critical comments on current advances in EVs derived from MSCs for wound repair, particularly elaborating on their impressive roles in effectively eliminating infections, inhibiting inflammation, promoting angiogenesis, and reducing scar formation. Last but not least, current limitations and future prospects of EVs derived from MSCs in the areas of wound repair are also objectively analyzed.

Automated summary

A skin wound is a rupture caused by external damage or underlying pathological conditions, and wound healing processes can be burdensome. Bacterial infection, inflammation, impaired angiogenesis, and scar formation hinder the recovery of skin wounds. Scientists are developing multifunctional nanomedicines to address these challenges. Mesenchymal stem cells (MSCs) have been explored for wound repair due to their self-renewal and multipotency, but immune concerns and legal restrictions need to be resolved. MSC-derived extracellular vesicles (EVs) are promising therapeutics for wound repair, possessing advantages such as abundant sources and convenient administration routes. However, current reviews lack focus on the specific roles of EVs in different stages of wound healing, making it necessary to highlight the significance of MSC-derived EVs in promoting wound healing. This review discusses the advances of MSC-derived EVs in wound repair, particularly their roles in eliminating infections, reducing inflammation, promoting angiogenesis, and minimizing scar formation. The limitations and future prospects of MSC-derived EVs in wound repair are also objectively analyzed.