Persistent High Glucose Concentrations Alter the Regenerative Potential of Mesenchymal Stem Cells

Abstract

Type 2 diabetes is associated with numerous long-term complications. This study aims to investigate whether impaired function of tissue-resident multipotent cells play role in pathogenesis of allied complications. Adipose-tissue-derived mesenchymal stem cells (ASCs) derived from nondiabetic (nASCs) and diabetic (dASCs) donors were compared with regard to glucose metabolism, cell replication, apoptosis, and differentiation potential. The data evidenced that elevation of glucose reduces proliferative capacity of both dASCs and nASCs, but impacts dASCs more significantly. Incorporation of insulin enhanced cell replication especially in nASCs. dASCs show higher levels of cellular senescence and apoptosis than nASCs. Unlike nASCs, apoptosis is induced via intrinsic pathway in dASCs. Data also evidenced that high glucose concentrations cause prominent disparities in nASCs and dASCs in expression of genes involved in insulin resistance such as adiponectin and resistin. Some changes in gene expression were irreversible in dASCs when treated with insulin. Additionally, high glucose concentrations reduce osteogenic and chondrogenic potential of ASCs, but enhance adipogenic potential. These results indicate that in addition to involvement in insulin resistance, impaired function of mesenchymal stem cells that reside in adipose tissue as one of the major sources of adult stem cells might be responsible for complications related to diabetes type 2.

Preserved β-Cell Function in Type 1 Diabetes by Mesenchymal Stromal Cells

“…Short-term expanded MSCs, as in the autologous setting, also elicit less innate immune attack when infused systemically, which supports their survival and function in vivo (24). There are reports of diabetesinduced changes in MSCs, including their regenerative potential, but these seem to mainly reflect effects of long-term hyperglycemia by, e.g., advanced glycation end products (25). In this study, we observed no defects in the expansion potential of MSCs after autologous harvest in subjects with recent-onset type 1 diabetes.…”

Safety and Effect of Adipose Tissue-Derived Stem Cell Implantation in Patients With Critical Limb Ischemia

“…30 In a rat diabetic model, MSC decreased osteogenic potential, 31 and exposure to high-glucose medium inhibited osteogenic differentiation and increased adipogenic differentiation in MG-63 osteosarcoma cells 32 and MSC. 33 Idei et al showed that the number of endothelial progenitor cells (EPC) and cell migration response to VEGF were significantly lower in atherosclerotic PAD patients compared to TAO patients, but the number and migration of EPC were similar between the TAO group and control group. 23 These results indicated that the functions of stem cells, including ATMSC, are compromised in diabetic patients.…”

Ectopic and Serum Lipid Levels Are Positively Associated with Bone Marrow Fat in Obesity

“…1 H MR spectroscopy might be used to identify patients at risk for bone loss. Further studies are needed to osteoblastogenesis of stem cells while enhancing adipogenesis (29). These results suggest that insulin resistance leads to increased marrow fat formation and concordant inhibition of osteoblast formation.…”