Combined treatment with bone marrow-derived mesenchymal stem cells and exendin-4 promotes islet regeneration in STZ-induced diabetic rats

Author(s):  
Xiaoyan Song ◽  
Xiaoya Sun ◽  
haojie hao ◽  
Qingwang Han ◽  
Weidong Han ◽  
...  
2013 ◽  
Vol 25 (05) ◽  
pp. 1340010 ◽  
Author(s):  
Wen-Tyng Li ◽  
Wen-Kai Hu ◽  
Feng-Ming Ho

Diabetes mellitus (DM) is associated with bone loss and leads to osteopenia and osteoporosis. This study was undertaken to investigate whether the impaired functions of mesenchymal stem cells (MSCs) derived from bone marrow play a role in pathogenesis of DM-associated bone loss. Bone marrow MSCs were taken from the alloxan-induced diabetic rats and normal rats. Bone mineral densities of tibias and femurs in diabetic rats decreased compared to those of normal rats as shown by dual energy X-ray absorptiometry. MSCs from diabetic rats exhibited reduced colony formation activity. The in vitro effects of high glucose (HG) (20 or 33 mM) on the growth, oxidative stress, apoptosis, and differentiation MSCs were next assessed. The viability and proliferation of MSCs derived from diabetic rats decreased significantly compared with that from normal rats. HG further suppressed the proliferation and viability of MSCs from both diabetic and normal rats. HG was associated with 38–40% increase in reactive oxygen species level and had significantly downregulated the activities of superoxide dismutase (SOD) and catalase (CAT) which could be recovered by the addition of L-ascorbic acid. The phenomena of apoptosis such as chromatin condensation and DNA fragmentation were found in cells cultured under HG conditions. As compared with 5.5 mM glucose, exposure of MSCs to HG enhanced adipogenic induction of triacylglycerol accumulation and inhibited osteogenic induction of alkaline phosphatase activity. HG increased peroxisome proliferator-activated receptor gamma expression during adipogenesis and reduced RUNX2 expression during osteoblastogenesis. These results indicate that MSCs derived from diabetic rats exhibited the inhibitory effects on cell growth and osteogenic ability. The oxidative stress, apoptosis, and adipogenic capability of MSCs were increased by HG. Furthermore, it is suggested that HG induces bone loss via attenuating the proliferation and osteoblastogenesis and enhancing adipogenesis mediated by the oxidative stress in rat bone marrow MSCs.


2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Jiangbo Wan ◽  
Liulu Xia ◽  
Wenjia Liang ◽  
Yi Liu ◽  
Qian Cai

In this paper, we established a delayed wound healing model on diabetic rat to mimic the pathophysiology of clinical patients who suffered from diabetic foot ulcers. We also evaluated if transplantation of allogeneic bone marrow-derived mesenchymal stem cells could promote the delayed wound healing and investigated the possible underlying biological mechanisms and stem cell behavior involved in this process. The results showed that bone marrow-derived mesenchymal stem cells had a positive effect on delayed wound healing in diabetic rats. Intramuscular transplantation demonstrated the best efficacy. This effect is associated with granulation tissue formation, angiogenesis, cellular proliferation, and high vascular endothelial growth factor expression in wound tissues. In addition, bone marrow-derived mesenchymal stem cells have been shown to mobilize and find home for ischemic and wounded tissues to participate in the process of wound healing. Intramuscular transplantation of exogenous isogeneic stem cells may be suitable for clinical application in the treatment of diabetic foot ulcers although the safety of this therapy should be considered.


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