Adipose Tissue-Derived Mesenchymal Stem Cells (ADMSCs) and ADMSC-Derived Secretome Expedited Wound Healing in a Rodent Model - A Preliminary Study

Hui Ma; Ping Kuen Lam; Wing Sum Siu; Cindy See Wai Tong; Kin Ki Yan Lo; Chi Man Koon; Xiao Xiao Wu; Xiang Li; Wen Cheng; Wai Ting Shum; Ping Chung Leung

doi:10.2147/CCID.S298105

Adipose Tissue-Derived Mesenchymal Stem Cells (ADMSCs) and ADMSC-Derived Secretome Expedited Wound Healing in a Rodent Model - A Preliminary Study

Clin Cosmet Investig Dermatol. 2021 Jun 30:14:753-764. doi: 10.2147/CCID.S298105. eCollection 2021.

Authors

Hui Ma^{1

2}, Ping Kuen Lam³, Wing Sum Siu^{1

2}, Cindy See Wai Tong³, Kin Ki Yan Lo³, Chi Man Koon^{1

2}, Xiao Xiao Wu^{1

2}, Xiang Li^{1

2}, Wen Cheng^{1

2}, Wai Ting Shum^{1

2}, Ping Chung Leung^{1

2}

Affiliations

¹ Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Region of China.
² State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Region of China.
³ Chow Tai Fook-Cheng Yu Tung Surgical Stem Cell Research Center, Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Region of China.

Abstract

Introduction: The biological role of mesenchymal stem cells (MSCs) in wound healing has been demonstrated. However, there were limited studies on the healing effect of secretome which consists of many biological factors secreted by MSCs. In this study, we aimed to compare the therapeutic effects of secretome with MSCs on facilitating wound healing.

Methods: Green fluorescent protein labelled adipose-derived MSCs (GFP-ADMSCs) or secretome was injected in the full-thickness skin excision model on SD rats. The wound healing process was evaluated by calculating the healing rate and the histological examinations on skin biopsy. The cell viability, proliferation and mobility of the rat dermal fibroblasts were compared after different treatments. The inflammatory response in macrophages was indicated by the level of nitric oxide (NO) and inflammatory cytokines through NO assay and ELISA.

Results: On day 5 and day 14, both MSCs and secretome accelerated the wound healing, secretome further enhanced the process. GFP-MSCs were detected 10 days after transplantation. The level of IL-6 and TNF-α in blood was reduced after MSCs and secretome treatments. The expressions of VEGF and PCNA were increased after treatment, higher intensity of VEGF was observed in secretome-injected tissue. The concentrations of total protein and VEGF in secretome were 2.2 ± 0.5 mg/mL and 882.0 ± 72.7 pg/mL, respectively. The cell viability and proliferation of FR were promoted significantly after the treatment. The scratch test showed that secretome accelerated the wound healing speed. Secretome reduced the metabolism of macrophages remarkably, but it did not decrease the level of macrophage-secreted NO. The expression of the pro-inflammatory cytokines (IL-6, MCP-1 and TNF-α) was downregulated significantly.

Conclusion: Our study indicated both MSCs and MSCs-derived secretome enhanced the wound healing process in early phase. Secretome further promoted the healing effects through promoting the fibroblast proliferation and migration and suppressing the inflammatory response.

Keywords: MSCs; local injection; secretome; skin; wound healing.