Exosomal microRNAs from Mesenchymal Stem Cells: Novel Therapeutic Effect in Wound Healing

Abstract

Background: Wound healing is a complicated biological process that leads to the regeneration of damaged skin tissue. Determining the methods to promote wound healing has become a hot topic in medical cosmetology and tissue repair research. Mesenchymal stem cells (MSCs) are a group of stem cells with the potential of self-renewal and multi-differentiation. MSCs transplantation has a broad application prospect in wound healing therapy. Many studies have demonstrated that the therapeutic capacity of MSCs is mainly mediated by paracrine actions. Exosomes (EXOs), which are nanosized vesicles carrying a variety of nucleic acids, proteins and lipids, are an important component of paracrine secretion. It has been demonstrated that exosomal microRNAs (EXO-miRNAs) play a key role in the function of exosomes.

Methods: In this review, we focus on current research on miRNAs from MSC-derived exosomes (MSC-EXO miRNAs) in terms of sorting, releasing and function and their effects on inflammation regulation, epidermal cell function, fibroblast function, and extracellular matrix formation. At last, we discuss the current attempts to improve the treatment of MSC-EXO-miRNAs.

Results: Many studies have demonstrated that MSC-EXO miRNAs play a key role in promoting wound healing. They have been shown to regulate inflammation response, enhance epidermal cell proliferation and migration, stimulate fibroblast proliferation and collagen synthesis, and regulate extracellular matrix formation. Besides, there have been a number of strategies developed to promote MSC-EXO and MSC-EXO miRNAs for wound healing treatment.

Conclusion: Utilizing the association of exosomes from MSCs with miRNAs may be a promising strategy to promote trauma healing. MSC-EXO miRNAs may provide a new approach to promote wound healing and improve the quality of life for patients with skin injuries.

Keywords: Exosome; Mesenchymal stem cells; Therapeutics; Wound healing; microRNA.

Fig. 1

Biogenesis, sorting, releasing and uptaking of miRNAs from MSC-derived exosomes. After miRNAs and EXOs are generated, some miRNAs specifically bind to RNA-binding proteins or membrane proteins according to specific motifs in miRNAs and are transported to EXOs by them. An RNA-binding proteins or membrane proteins can bind to different miRNAs with the same motifs. An RNA-binding proteins or membrane proteins also bind to more than one motif miRNA. EXOs are released extracellular through exocytosis, and miRNA can be protected from extracellular degradation under the protection of EXOs. Recipient cells absorb released EXOs through three mechanisms. (1) Direct fusion with the plasma membrane, (2) Phagocytosis, (3) Receptor-mediated endocytosis

Fig. 2

The current and future direction of exosomal miRNAs. Now many researchers are studying and future directions will focus on efficacy and specificity, delivery, safety, quality and production. How to design suitable miRNA promoters and miRNA inhibitors, and how to use gene modification to make MSC-exos more effective and safer. To further explore the mechanism of exosomeal miRNA, conduct in vivo and in vitro experiments to prepare for clinical use. In terms of safety, immunogenicity, tumorigenicity and toxicity should be concerned, and the optimal dose, route of administration schedule and route of administration should be determined. Quality consistency and mass production capacity require constant attention, and remarkable results have been achieved so far. Strategies for Delivering Cells/EXOs currently include cell spray, infusing, injection, hydrogel, matrix carrier, bioprinting, scaffold-guided delivery, engineered skin substitute