Low-glucose culture environment can enhance the wound healing capability of diabetic adipose-derived stem cells

Abstract

Background Application of autologous adipose-derived stem cells (ASC) for diabetic chronic wounds has become an emerging treatment option. However, ASCs from diabetic individuals showed impaired cell function and suboptimal wound healing effects. We proposed that adopting a low-glucose level in the culture medium for diabetic ASCs may restore their pro-healing capabilities. Methods ASCs from diabetic humans and mice were retrieved and cultured in high-glucose (HG, 4.5 g/L) or low-glucose (LG, 1.0 g/L) conditions. Cell characteristics and functions were investigated in vitro. Moreover, we applied diabetic murine ASCs cultured in HG or LG condition to a wound healing model in diabetic mice to compare their healing capabilities in vivo. Results Human ASCs exhibited decreased cell proliferation and migration with enhanced senescence when cultured in HG condition in vitro. Similar findings were noted in ASCs derived from diabetic mice. The inferior cellular functions could be partially recovered when they were cultured in LG condition. In the animal study, wounds healed faster when treated with HG- or LG-cultured diabetic ASCs relative to the control group. Moreover, higher collagen density, more angiogenesis and cellular retention of applied ASCs were found in wound tissues treated with diabetic ASCs cultured in LG condition. Conclusions In line with the literature, our study showed that a diabetic milieu exerts an adverse effect on ASCs. Adopting LG culture condition is a simple and effective approach to enhance the wound healing capabilities of diabetic ASCs, which is valuable for the clinical application of autologous ASCs from diabetic patients.

Dual Glyoxalase-1 and β-Klotho Gene-Activated Scaffold Reduces Methylglyoxal and Reprograms Diabetic Adipose-Derived Stem Cells: Prospects in Improved Wound Healing

“…It involves the spatial and temporal synchronization of a variety of cell types, extracellular matrix proteins (ECM) and growth factors with distinct roles in the phases of hemostasis [ 44 ]. Stem cells serve as vehicles for the delivery of growth factors and cytokines to the wound site, thereby promoting the migration of other cell types which transiently stream through phases of wound healing [ 13 , 14 ]. A hyperglycemic environment impairs wound healing as well as mediates the diabetic stem cells to a senescent stage with dADSCs displaying poor angiogenic properties [ 12 , 16 ].…”

“…Adipose-derived stem cells (ADSCs) represent mesenchymal stem cells derived from the mesoderm and ADSC tissue regeneration therapy has shown promising results in comparison to other stem cells due to low donor site morbidity rates, fewer incidences of complications, their potential to differentiate into different cell types and wound healing cytokine production [ 9 , 10 , 11 , 12 ]. ADSCs have been widely used in tissue engineering and have shown promising results both in vitro and in vivo in reducing fibrosis, wherein stem cell-conditioned media have been reported to inhibit the TGF-β1-induced differentiation of keloid and hypertrophic scar-derived fibroblasts [ 13 , 14 ]. However, in a hyperglycemic environment, dADSCs shows greater senescence with poor angiogenic properties resulting in slower wound activation in DFUs [ 1 , 15 ].…”

Optimization strategies for mesenchymal stem cell-based analgesia therapy: a promising therapy for pain management

“…Hormones such as insulin and glucagon play a vital role in regulating blood glucose levels in healthy individuals, maintaining it at around 1 mg/mL. When MSCs are exposed to a high glucose medium of 4.5 mg/mL, it results in significant inhibition of proliferation and cell senescence [ 66 ]. Additionally, a high glucose medium promotes osteogenic differentiation but weakens the chondrogenic capacity of MSCs [ 67 ].…”