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

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

  • Stem Cell Res Ther. 2021 Aug 3;12(1):434. doi: 10.1186/s13287-021-02517-0.
Yan Zhang 1 2,  Yingjin Pan 3,  Yanhong Liu 4,  Xiheng Li 1 2,  Liang Tang 1 2,  Mengna Duan 5,  Jiang Li 6 7,  Guokun Zhang 8 9
Affiliations

Affiliations

  • 1 Hospital of Stomatology, Jilin University, 1500 Qinghua Rd., Changchun, Jilin, 130021, China.
  • 2 Jilin Provincial Laboratory of Biomedical Engineering, Jilin University, Changchun, China.
  • 3 Center of Prosthodontics and Oral Implantology, Foshan Stomatology Hospital, School of Stomatology and Medicine, Foshan University, Foshan, 528000, China.
  • 4 Center for Reproductive Medicine, Center for Prenatal Diagnosis, First Hospital, Jilin University, Changchun, China.
  • 5 Hospital of Stomatology, Jilin University, 1500 Qinghua Rd., Changchun, Jilin, 130021, China. dmnmengna@jlu.edu.cn.
  • 6 Hospital of Stomatology, Jilin University, 1500 Qinghua Rd., Changchun, Jilin, 130021, China. ljiang@gzhmu.edu.cn.
  • 7 Affiliated Stomatology Hospital of Guangzhou Medical University, 39 Huangsha Ave., Guangzhou, 510080, Guangdong, China. ljiang@gzhmu.edu.cn.
  • 8 Institute of Antler Science and Product Technology, Changchun Sci-Tech University, 1345 Pudong Rd., Changchun, Jilin, 130600, China. zhang-guokun@hotmail.com.
  • 9 Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences (CAAS), 4899 Juye St., Changchun, Jilin, 130112, China. zhang-guokun@hotmail.com.
PMID: 34344478 DOI: 10.1186/s13287-021-02517-0
Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords

Cord blood stem cell transplantation; Exosomes; MicroRNAs; Myofibroblasts; Regeneration; Transforming growth factor beta; Wound healing.

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