Mesenchymal stromal cells-exosomes: a promising cell-free therapeutic tool for wound healing and cutaneous regeneration

Abstract

Cutaneous regeneration at the wound site involves several intricate and dynamic processes which require a series of coordinated interactions implicating various cell types, growth factors, extracellular matrix (ECM), nerves, and blood vessels. Mesenchymal stromal cells (MSCs) take part in all the skin wound healing stages playing active and beneficial roles in animal models and humans. Exosomes, which are among the key products MSCs release, mimic the effects of parental MSCs. They can shuttle various effector proteins, messenger RNA (mRNA) and microRNAs (miRNAs) to modulate the activity of recipient cells, playing important roles in wound healing. Moreover, using exosomes avoids many risks associated with cell transplantation. Therefore, as a novel type of cell-free therapy, MSC-exosome -mediated administration may be safer and more efficient than whole cell. In this review, we provide a comprehensive understanding of the latest studies and observations on the role of MSC-exosome therapy in wound healing and cutaneous regeneration. In addition, we address the hypothesis of MSCs microenvironment extracellular vesicles (MSCs-MEVs) or MSCs microenvironment exosomes (MSCs-MExos) that need to take stock of and solved urgently in the related research about MSC-exosomes therapeutic applications. This review can inspire investigators to explore new research directions of MSC-exosome therapy in cutaneous repair and regeneration.

Keywords: Cutaneous regeneration; Exosomes; Mesenchymal stromal cell; Microenvironment; Wound healing.

Fig. 1

Under the stimulating human umbilical cord-derived mesenchymal stromal cells (hUC-dMSCs) with different factors, the quantities and components of exosomes had changed. Then, the biological characteristics of target cells also have changed after received the exosomes. (a) In a normal situation, target cells receive microvesicles and exosomes released from MSCs. (b) Stimulating hUC-dMSCs with interferon (IFN)- g, there were in a simulated inflammatory microenvironment that can significantly increase the release of MSCs-exosomes. Then, it can enhance the immunomodulatory activity of hUC-discs and increase the proportion of CD4+, CD25+ and Foxp3+T cells in the entire regulatory T cells. (c) Stimulating hUC-dMSCs with lipopolysaccharide (LPS) can secrete more exosomes than untreated ones, and the exosome derived from them are rich in miRNA let-7b, which can induce macrophages to exhibit the anti-inflammatory M2 phenotype by the specific signal pathway

Fig. 2

With the changing of culture environment, the components of mesenchymal stromal cell - extracellular vesicles (MSCs-EVs) or MSCs-exosomes also have changed. IFN interferon, IL interleukin, TGF transforming growth factor, TNF , tumor necrosis factor, VEGF vascular endothelial growth factor, α-SMA α-smooth muscle actin