The application of mesenchymal stromal cells (MSCs) and their derivative exosome in skin wound healing: a comprehensive review

Abstract

Recently, mesenchymal stromal cells (MSCs) and also their exosome has become a game-changing tool in the context of tissue engineering and regenerative medicine. MSCs due to their competencies to establish skin cells, such as fibroblast and keratinocyte, and also their unique attribute to suppress inflammation in wound site has attracted increasing attention among scholars. In addition, MSC’s other capabilities to induce angiogenesis as a result of secretion of pro-angiogenic factors accompanied with marked anti-fibrotic activities, which mainly mediated by the releases matrix metalloproteinase (MMPs), make them a rational and effective strategy to accelerate wound healing with a small scar. Since the chief healing properties of the MSCs depend on their paracrine effects, it appears that MSCs-derived exosomes also can be an alternative option to support wound healing and skin regeneration as an innovative cell-free approach. Such exosomes convey functional cargos (e.g., growth factor, cytokine, miRNA, etc.) from MSCs to target cells, thereby affecting the recipient skin cells’ biological events, such as migration, proliferation, and also secretion of ECM components (e.g., collagen). The main superiorities of exosome therapy over parental MSCs are the diminished risk of tumor formation and also lower immunogenicity. Herein, we deliver an overview of recent in vivo reports rendering the therapeutic benefits of the MSCs-based therapies to ease skin wound healing, and so improving quality of life among patients suffering from such conditions.

Mesenchymal Stem Cell Application and Its Therapeutic Mechanisms in Intracerebral Hemorrhage

“…Some studies have verified that MSCs can be isolated from various adult tissues such as the bone marrow, adipose tissue, synovium, and neonatal tissues, including the umbilical cord (blood), placenta, amniotic fluid, and amniotic membrane, and possess the potential of differentiating into diverse cell lineages and tissues like bone, adipose tissue, cartilage, nerves, and liver, both in vivo and in vitro ( Gao et al, 2018 ; Sumer et al, 2018 ; Mathot et al, 2019 ; Gong et al, 2021 ; Li J. et al, 2021 ; Li Q. Y. et al, 2021 ; Ramesh et al, 2021 ; Souza et al, 2021 ; Zhu et al, 2021 ; Bian et al, 2022 ). Others have verified that MSC treatment holding promise exerts indirect therapeutic mechanisms such as anti-inflammation ( Huang et al, 2019 ), secretion of growth factors ( Tang W. et al, 2021 ; Ulpiano et al, 2021 ), and EVs ( Bang and Kim, 2022 ), which are associated with the recovery of damaged tissues.…”

Fibroblasts in Scar Formation: Biology and Clinical Translation

“…Regarding their last strategy, exosomes comprising mRNAs, miRNAs, cytokines, and growth factors are isolated, and their effects on the behavior of fibroblasts are evaluated. The use of exosomes also exerts promising clinical translation [ 11 ]. For example, transplantation of exosomes from the human umbilical cord blood plasma (UCB-Exos) accelerates cutaneous wound healing through miR-21-3p-mediated promotion of angiogenesis and fibroblast function [ 107 ].…”

“…Additionally, differentiation towards cancer-associated fibroblasts (CAFs) may have an adverse function in skin healing. Yet, given the rapid development of nanotechnology, the use of nanodrugs may facilitate scar-free wound healing [ 11 , 12 ].…”

Self-Assembled Nano-Peptide Hydrogels with Human Umbilical Cord Mesenchymal Stem Cell Spheroids Accelerate Diabetic Skin Wound Healing by Inhibiting Inflammation and Promoting Angiogenesis

“…The strong paracrine capability of MSCs provides a new approach to tissue repair. 25 Previous studies reported that a combination of stem cells and vector biomaterials jointly constituted a growth pattern conformed to the internal environment of the human body; thus, greatly improving the survival rate and proliferation efficiency of MSCs, and significantly enhancing their secretory properties. 26 , 27 There have been a number of studies on the tissue engineering of vector biomaterials, mainly involving bio-ceramics, alginate, chitosan, and hydrogels.…”