Adipose mesenchymal stem cell‐derived exosomes promote cell proliferation, migration, and inhibit cell apoptosis via Wnt/β‐catenin signaling in cutaneous wound healing

Abstract

Cutaneous wounds, a type of soft tissue injury, are difficult to heal in aging. Differentiation, migration, proliferation, and apoptosis of skin cells are identified as key factors during wound healing processes. Mesenchymal stem cells have been documented as possible candidates for wound healing treatment because their use could augment the regenerative capacity of many tissues.However, the effects of exosomes derived from adipose-derived stem cell (ADSC-exos) on cutaneous wound healing remain to be carefully elucidated. In this present study, HaCaT cells were exposed to hydrogen peroxide (H 2 O 2 ) for the establishment of the skin lesion model. Cell Counting Kit-8 assay, migration assay, and flow cytometry assay were conducted to detect the biological function of ADSC-exos in skin lesion model. Finally, the possible mechanism was further investigated using Western blot assay. The successful construction of the skin lesion model was confirmed by results of the enhanced cell apoptosis of HaCaT cells induced by H 2 O 2 , the increased Bax expression and decreased Bcl-2 expression. CD9 and CD63 expression evidenced the existence of ADSCexos. The results of functional experiments demonstrated that ADSC-exos could prompt cell proliferation and migration of HaCaT cells, and repress cell apoptosis of HaCaT cells. In addition, the activation of Wnt/β-catenin signaling was confirmed by the enhanced expression of β-catenin at the protein level.Collectively, our findings suggest that ADSC-exos play a positive role in cutaneous wound healing possibly via Wnt/β-catenin signaling. Our study may provide new insights into the therapeutic target for cutaneous wound healing. K E Y W O R D Sadipose-derived stem cell, exosomes, Wnt/β-catenin, wound healing

Comparison of Proangiogenic Effects of Adipose-Derived Stem Cells and Foreskin Fibroblast Exosomes on Artificial Dermis Prefabricated Flaps

“…The size of exosomes can be identified by TEM and NTA, and proteins such as CD63, CD81, TSG101, and HSP70, which are usually rich in exosomes, can be identified by western blot [15]. Numerous recent studies [38][39][40] showed that mesenchymal stem cell-derived exosomes (MSC-Exo) promoted the repair of tissue damage, leading to great progress in wound repair. MSC-…”

“…Exo were also shown to induce the proliferation and migration of vascular endothelial cells, promote angiogenesis, and reduce apoptosis of endothelial cells, indicating important roles in injury repair and vascularization [10,39]. In the current study, we therefore applied ADSC-Exo to artificial dermal prefabricated flaps to overcome the issue of insufficient vascularization.…”

Exosomes From Adipose-Derived Stem Cells: The Emerging Roles and Applications in Tissue Regeneration of Plastic and Cosmetic Surgery

“…Studies have shown that ASC-exos played a positive role in cutaneous wound healing by means of acting on HDFs and HaCaTs and other main target cells through various signal channels ( Figure 1C; Qiu et al, 2020). Ma et al (2019) exposed HaCaTs to hydrogen peroxide (H 2 O 2 ) for establishing a skin lesion model, discovering that ASC-exos could foster HaCaTs proliferation, migration, and inhibit apoptosis through Wnt/β-catenin signaling pathway. Likewise, He et al (2020) also confirmed that MALAT1-containing ASC-exos improved wound healing by targeting miR-124 and activating Wnt/β-catenin pathway.…”

Secretome of Adipose Tissue-Derived Stem Cells (ASCs) as a Novel Trend in Chronic Non-Healing Wounds: An Overview of Experimental In Vitro and In Vivo Studies and Methodological Variables

“…On the other hand, levels of ROS and inflammatory cytokines were significantly decreased by treatment with ASC-Exos. Using HaCaT cells exposed to hydrogen peroxide (H 2 O 2 ) for the establishment of a skin lesion model, Ma et al [83] explored the effects of Exos derived from human facial adipose tissue on cell proliferation assessed by the cell counting kit (CCK)-8 assay, and the migration rate analyzed with standard scratch wound healing and transwell assays. Exos were extracted from 24 h ASC-CM using a commercial exosome isolation reagent, characterized with TEM for the morphology and size (30-100 nm).…”

“…induced apoptosis levels [83]. ASC: adipose tissue-derived stem cell; HMEC: human mammary epithelial cell; HDF: human dermal fibroblast; HUVEC: human umbilical vein endothelial cell; Akt: protein kinase B; PI3K: phosphoinositide 3-kinase; ERK: extracellular signal-regulated kinase; HaCaT: spontaneously immortalized human keratinocyte cell line.…”