Diabetes impairs adipose tissue–derived stem cell function and efficiency in promoting wound healing

Abstract

Adipose tissue-derived stem cells (ASCs) are gaining increasing consideration in tissue repair therapeutic application. Recent evidence indicates that ASCs enhance skin repair in animal models of impaired wound healing. To assess the therapeutic activity of autologous vs. allogeneic ASCs in the treatment of diabetic ulcers, we functionally characterized diabetic ASCs and investigated their potential to promote wound healing with respect to nondiabetic ones. Adipose tissue-derived cells from streptozotocin-induced type 1 diabetic mice were analyzed either freshly isolated as stromal vascular fraction (SVF), or following a single passage of culture (ASCs). Diabetic ASCs showed decreased proliferative potential and migration. Expression of surface markers was altered in diabetic SVF and cultured ASCs, with a reduction in stem cell marker-positive cells. ASCs from diabetic mice released lower amounts of hepatocyte growth factor, vascular endothelial growth factor (VEGF)-A, and insulin-like growth factor-1, growth factors playing important roles in skin repair. Accordingly, the supernatant of diabetic ASCs manifested reduced capability to promote keratinocyte and fibroblast proliferation and migration. Therapeutic potential of diabetic SVF administered to wounds of diabetic mice was blunted as compared with cells isolated from nondiabetic mice. Our data indicate that diabetes alters ASC intrinsic properties and impairs their function, thus affecting therapeutic potential in the autologous treatment for diabetic ulcers.

Allogeneic Transplantation of an Adipose-Derived Stem Cell Sheet Combined With Artificial Skin Accelerates Wound Healing in a Rat Wound Model of Type 2 Diabetes and Obesity

“…Furthermore, after obtaining autologous ASCs, ASC sheet preparation requires several weeks. rASCs from diabetic animals exhibit altered properties and impaired functions (40). In fact, our group attempted to create rASC sheets using rASCs from ZDF rats, but cell proliferation was slow (data not shown).…”

Progenitor Cell Dysfunctions Underlie Some Diabetic Complications

“…In the skin, for example, population-based studies of transplanted diabetic adipose-derived stem cells (ASCs) from mice demonstrate decreased proliferation, migration, and growth factor production, with an inability to promote keratinocyte and fibroblast proliferation and migration. 66 However, stem cells and progenitor cells are complex cell populations associated with functional heterogeneity. Traditional population-level assays, such as microarray or immunoblotting, that involve pooling of RNA or protein from hundreds of thousands of cells report aggregate expression of data.…”

A Cautionary Tale for Autologous Vascular Tissue Engineering: Impact of Human Demographics on the Ability of Adipose-Derived Mesenchymal Stem Cells to Recruit and Differentiate into Smooth Muscle Cells

“…While taken together, these studies have shown that cellularizing tissue-engineered grafts significantly improves the patency and regeneration over their acellular counterparts; these models hold limited relevance for clinical translation since in practice, cells would need to be harvested from patients at high cardiovascular risk such as diabetics 64,65 and the elderly. [66][67][68] In addition, these high-risk groups possess pathologic conditions such as a hyperglycemic environment [69][70][71][72] and ageassociated senescence, [73][74][75][76][77][78][79][80][81][82][83][84][85] respectively, which can decrease the ability of their stem cells to proliferate, differentiate into specific mesenchymal cell types, and promote angiogenesis. Whereas bone marrow has been shown to be a source of stem cells, it is particularly important to consider the use of adipose-derived mesenchymal stem cells (AD-MSCs) due to their ease of isolation and abundance.…”