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

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.

Secretome from human adipose-derived mesenchymal stem cells promotes blood vessel formation and pericyte coverage in experimental skin repair

“…Hypoxic preconditioning is one of the most frequent ways to improve hASC secretome, as hypoxic stress reduces oxygen, improves cellular function, and increases the concentration of paracrine factors [16,17] that promotes wound healing [18][19][20][21] with fewer scar formation [22][23][24] in comparison to normoxic conditions. Furthermore, hASCs secretome produced in serum-free media has enhanced immunosuppressive and anti-fibrotic abilities because of increased vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) secretion [25,26]. These findings led us to the hypothesis that serum-free media and hypoxic preconditioning would synergistically enhance the therapeutic effects of hASCs secretome on wound healing.…”

Enhancing Stem Cell-Based Therapeutic Potential by Combining Various Bioengineering Technologies

“…Adipose tissue derived (AD)-MSCs or secretome significantly enhanced the healing process in early phase by increasing the migration and proliferation of dermal fibroblasts and inhibiting the inflammatory response ( Ma et al, 2021 ). These intracutaneously injected AD-MSCs at the dermal and subcutaneous layers can survive in vivo for up to 1 year in immunodeficient mice and differentiate into adipocytes to provide architectural support and microenvironment for re-epithelialization and subsequent dermal repair ( Koellensperger et al, 2014 ).…”

The Application of Adipose Tissue-Derived Mesenchymal Stem Cells (ADMSCs) and a Twin-Herb Formula to the Rodent Wound Healing Model: Use Alone or Together?

“…Mesenchymal stem cells (MSCs), first isolated in the 1970s, are a group of progenitor cells of mesodermal source. They present a high self-renewing capacity and various linage differentiation abilities [ 9 ]. They are widely used in the study of wound care management, bone and cartilage diseases, cardiovascular and neurological diseases, and immune-/inflammation-mediated diseases [ 10 ].…”