Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulate regenerative wound healing via transforming growth factor-β receptor inhibition

• Published in: Stem cell research & therapy Vol. 12; no. 1; p. 434
• Main Authors: Zhang, Yan, Pan, Yingjin, Liu, Yanhong, Li, Xiheng, Tang, Liang, Duan, Mengna, Li, Jiang, Zhang, Guokun
• Format: Journal Article
• Language: English
• Published: England BioMed Central 03.08.2021; BMC
• Subjects: Animals; Antibodies; Cell culture; Cell migration; Cell proliferation; Collagen; Collagen (type I); Cord blood; Cord blood stem cell transplantation; Exosomes; Fetal Blood; Fibroblasts; Humans; Mesenchymal Stem Cells; MicroRNAs; MicroRNAs - genetics; miRNA; Myofibroblasts; Nerves; Rats; Receptor, Transforming Growth Factor-beta Type II; Receptors, Transforming Growth Factor beta - genetics; Regeneration; Scars; Signal transduction; Skin; Stem cell transplantation; Stem cells; Transforming growth factor beta; Transforming growth factor-b; Transforming growth factor-b1; Transforming Growth Factors; Umbilical cord; Wound Healing; United States > US; China; Regeneration; Wound healing; Cord blood stem cell transplantation; MicroRNAs; Myofibroblasts; Exosomes; Transforming growth factor beta
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-021-02517-0

Scar formation is a common consequence of skin wound healing, and no effective treatment exists. Umbilical cord blood mesenchymal stem cells (UCB-MSCs) can improve wound healing; however, the role of UCB-MSCs remains unclear and whether they can ameliorate scar formation has not been fully elucidated. To determine the function of UCB-MSCs, we examined and compared the therapeutic effects of UCB-MSCs and UCB-MSC-derived exosomes (UCB-MSC-exo) on skin healing in rats. Moreover, UCB-MSC-exo-specific miRNAs were identified and their effects in inhibiting the human dermal fibroblast (HDF) differentiation into myofibroblasts were investigated. Both UCB-MSCs and UCB-MSC-exo accelerated wound closure; reduced scar formation; improved the regeneration of skin appendages, nerves, and vessels; and regulated the natural distribution of collagen fibers in wound healing. Additionally, UCB-MSC-exo suppressed the excessive formation of myofibroblasts and collagen I and increased the proliferation and migration of skin cells in vivo and in vitro. Functional analysis showed that UCB-MSC-derived miRNAs were closely related to the transforming growth factor-β (TGF-β) signaling pathway, which could induce myofibroblast differentiation. We identified abundant miRNAs that were highly expressed in UCB-MSC-exo. miR-21-5p and miR-125b-5p were predicted to contribute to TGF-β receptor type II (TGFBR2) and TGF-β receptor type I (TGFBR1) inhibition, respectively. Using miRNA mimics, we found that miR-21-5p and miR-125b-5p were critical for anti-myofibroblast differentiation in the TGF-β1-induced HDF. The effect of UCB-MSCs in stimulating regenerative wound healing might be achieved through exosomes, which can be, in part, through miR-21-5p- and miR-125b-5p-mediated TGF-β receptor inhibition, suggesting that UCB-MSC-exo might represent a novel strategy to prevent scar formation during wound healing.