Experimental Type 2 Diabetes Differently Impacts on the Select Functions of Bone Marrow-Derived Multipotent Stromal Cells

Abstract

Bone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modality for cell therapy in type 2 diabetes mellitus (T2DM)-associated complications. T2DM changes the bone marrow environment; however, its effects on BMMSC properties remain unclear. The present study aimed at investigating select functions and differentiation of BMMSCs harvested from the T2DM microenvironment as potential candidates for regenerative medicine. BMMSCs were obtained from Zucker diabetic fatty (ZDF; an obese-T2DM model) rats and their lean littermates (ZL; controls), and cultured under normoglycemic conditions. The BMMSCs derived from ZDF animals were fewer in number, with limited clonogenicity (by 2-fold), adhesion (by 2.9-fold), proliferation (by 50%), migration capability (by 25%), and increased apoptosis rate (by 2.5-fold) compared to their ZL counterparts. Compared to the cultured ZL-BMMSCs, the ZDF-BMMSCs exhibited (i) enhanced adipogenic differentiation (increased number of lipid droplets by 2-fold; upregulation of the Pparg, AdipoQ, and Fabp genes), possibly due to having been primed to undergo such differentiation in vivo prior to cell isolation, and (ii) different angiogenesis-related gene expression in vitro and decreased proangiogenic potential after transplantation in nude mice. These results provided evidence that the T2DM environment impairs BMMSC expansion and select functions pertinent to their efficacy when used in autologous cell therapies.

Characterisation and Expression of Osteogenic and Periodontal Markers of Bone Marrow Mesenchymal Stem Cells (BM-MSCs) from Diabetic Knee Joints

“…In contrast, BM-MSCs cultured under high glucose (HG) [ 38 ] or other diabetes simulation conditions such as a combination of HG and palmitic acid [ 39 ] or advanced glycated endproducts (AGEs) [ 40 ] showed significantly lower proliferation capacities. Such studies usually use nonphysiological high concentrations of glucose [ 41 ] and may not fully replicate the T2DM microenvironment that entails hyperglycaemia as well as high levels of AGEs, reactive oxygen species (ROS), hyperlipidaemia, hyperinsulinemia and inflammatory cytokines [ 42 ].…”

mTOR Signaling Pathway in Bone Diseases Associated with Hyperglycemia

“…The vascular components within the skeletal system play a vital role in regulating bone metabolism by facilitating the necessary supply of nutrients and biochemical factors, mobilizing bone progenitor cells, and balancing osteogenesis and osteolysis [119]. Diseased conditions such as DM have been shown to negatively impact the expression of angiogenesis-related genes in the skeletal system and impair BMSCs and pericyte functionality, leading to pro-angiogenic dysfunction [120][121][122]. T1DM mice demonstrated vascular lesions in bone, especially damage to type H blood vessels, which are responsible for coupling vascularization with osteogenesis [123], while the reduced microvascular blood flow in T2DM patients was notably linked to elevated cortical bone porosity [124].…”

Osteogenic differentiation potential by mouse bone marrow-derived mesenchymal stemcells (mbm-mscs) derived from gut leak-induced diabetes type ii mouse model

“…Our result presented the similarity to Wang et al (2013) research which demonstrated the high glucose condition caused increase the growth of MSCs but decrease MSCs mineralization on mBM-MSCs derived from C57BL/6 mice. Moreover, Ribot et al (2021) study of rat BM-MSCs derived from diabetes type II rat model, the normoglycemic condition showed that despite cultured in normoglycemic condition, rat BM-MSCs still expressed elevated reactive oxygen species (ROS) level due to diabetes type II environment permanently affected cellular ROS production. In addition, elevated level of ROS in MSCs were known to inhibit the osteogenic differentiation (Chen et al, 2008;Denu and…”