Abstract
BackgroundDiabetic patients suffer from impaired wound healing. Mesenchymal stem cell (MSC) therapy represents a promising approach toward improving skin wound healing through the release of soluble growth factors and cytokines that stimulate new vessel formation and modulate inflammation. Whether adipose tissue-derived MSCs (ASCs) from type 2 diabetes (T2D) donors are suitable for skin damage repair remains largely unknown.MethodsIn this study, we compared the phenotype and functionality of ASCs harvested from high-fat diet (HFD) and streptozotocin (STZ)-induced T2D or control mice, and assessed their abilities to promote wound healing in an excisional wound splinting mouse model with T2D.ResultsT2D ASCs expressed similar cellular markers as control ASCs but secreted less hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and transforming growth factor β (TGF-β). T2D ASCs were somewhat less effective in promoting healing of the wound, as manifested by slightly reduced re-epithelialization, cutaneous appendage regeneration, and collagen III deposition in wound tissues. In vitro, T2D ASCs promoted proliferation and migration of skin fibroblasts to a comparable extent as control ASCs via suppression of inflammation and macrophage infiltration.ConclusionsFrom these findings, we conclude that, although ASCs from T2D mice are marginally inferior to control ASCs, they possess comparable therapeutic effects in wound healing.
Highlights
Type 2 diabetes (T2D) is a metabolic disease characterized by insulin resistance and pancreatic β cell dysfunction, which results in long-term hyperglycemia and various degenerative complications [1]
Our most dramatic finding was that type 2 diabetes (T2D) adipose tissuederived MSCs (ASCs) were effective in promoting wound healing, the efficiency was lower than ASCs harvested from healthy, age-matched control mice
T2D ASCs secreted lower amount of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and transforming growth factor β (TGF-β), three major cytokines that mediate the protective effects of ASCs, which might have affected the therapeutic effect of T2D ASCs in wound healing
Summary
Type 2 diabetes (T2D) is a metabolic disease characterized by insulin resistance and pancreatic β cell dysfunction, which results in long-term hyperglycemia and various degenerative complications [1]. Sun et al Stem Cell Research & Therapy (2020) 11:298. MSCs are adult stem cells that can be harvested from multiple tissues including bone marrow, adipose tissue, and umbilical cord [8]. Transplantation of MSCs alone or in combination with biological scaffolds significantly promotes wound healing [10,11,12,13]. MSCs from various sources have been shown to effectively promote wound healing. Mesenchymal stem cell (MSC) therapy represents a promising approach toward improving skin wound healing through the release of soluble growth factors and cytokines that stimulate new vessel formation and modulate inflammation. Whether adipose tissuederived MSCs (ASCs) from type 2 diabetes (T2D) donors are suitable for skin damage repair remains largely unknown
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