High glucose-induced reactive oxygen species generation promotes stemness in human adipose-derived stem cells
Journal
Cytotherapy
Journal Volume
18
Journal Issue
3
Pages
371-383
Date Issued
2016
Author(s)
Abstract
Background aims Adipose-derived stem cells (ASCs) represent an important source of cell therapy to treat diabetic complications. However, hyperglycemia may alter several cellular functions, so the present study aimed to investigate the influence of a diabetic environment on the stemness and differentiation capabilities of ASCs. Methods Human ASCs were obtained from subcutaneous adipose tissues of diabetic (dASCs) and nondiabetic donors (nASCs) and characterized. To reproduce an in vitro hyperglycemia environment, the nASCs were also cultured under prolonged high-glucose (HG; 4.5 g/L) or low-glucose (LG; 1.0 g/L) conditions. Results The expression of cell surface markers in dASCs and nASC was similar and characteristic of mesenchymal stem cells. Although dASCs or HG-treated nASCs exhibited decreased proliferation, enhanced expression of the pluripotent markers Sox-2, Oct-4, and Nanog was observed. Moreover, HG-treated nASCs exhibited decreased cell migration, enhanced senescence, and significantly higher intracellular reactive oxygen species (ROS), whereas their adipogenic and osteogenic differentiation capacities remained comparable to LG-treated cells. With antioxidant treatment, HG-treated nASCs showed improved cell proliferative activity without stemness enhancement. This HG-induced biological response was associated with ROS-mediated AKT attenuation. When cultured in an appropriate induction medium, the HG-treated nASCs and dASCs exhibited enhanced potential of transdifferentiation into neuron-like cells. Discussion Despite lower proliferative activity and higher senescence in a diabetic environment, ASCs also exhibit enhanced stemness and neurogenic transdifferentiation potential via a ROS-mediated mechanism. The information is important for future application of autologous ASCs in diabetic patients. ? 2015 International Society for Cellular Therapy.
Other Subjects
antioxidant; cell surface marker; glucose; octamer transcription factor 4; protein kinase B; reactive oxygen metabolite; transcription factor NANOG; transcription factor Sox2; biological marker; glucose; reactive oxygen metabolite; adipose derived stem cell; adult; aged; Article; cell aging; cell differentiation; cell migration; cell transdifferentiation; cellular parameters; clinical article; controlled study; diabetes mellitus; diabetic patient; gene expression; human; human cell; hyperglycemia; in vitro study; mesenchymal stem cell; middle aged; nerve cell; osteosarcoma cell; pluripotent stem cell; priority journal; stem cell stemness; subcutaneous fat; adipocyte; bone development; case control study; cell culture; cell proliferation; complication; cytology; drug effects; mesenchymal stroma cell; metabolism; non insulin dependent diabetes mellitus; pathology; physiology; Adipocytes; Adult; Aged; Biomarkers; Case-Control Studies; Cell Differentiation; Cell Proliferation; Cell Transdifferentiation; Cells, Cultured; Diabetes Mellitus, Type 2; Glucose; Humans; Hyperglycemia; Mesenchymal Stromal Cells; Middle Aged; Osteogenesis; Reactive Oxygen Species; Subcutaneous Fat
Publisher
Taylor and Francis Ltd
Type
journal article