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Stem Cells Transl Med. 2017 Jan;6(1):261-271. doi: 10.5966/sctm.2015-0380. Epub 2016 Aug 15.

Glyoxalase-1 Overexpression Reverses Defective Proangiogenic Function of Diabetic Adipose-Derived Stem Cells in Streptozotocin-Induced Diabetic Mice Model of Critical Limb Ischemia.

Author information

1
Department of Vascular Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China.
2
Vascular Center of Shanghai JiaoTong University, Shanghai, People's Republic of China.

Abstract

Adipose-derived stem cell (ADSC)-based therapy is promising for critical limb ischemia (CLI) treatment, especially in patients with diabetes. However, the therapeutic effects of diabetic ADSCs (D-ADSCs) are impaired by the diabetes, possibly through intracellular reactive oxygen species (ROS) accumulation. The objective of the present study was to detect whether overexpression of methylglyoxal-metabolizing enzyme glyoxalase-1 (GLO1), which reduces ROS in D-ADSCs, can restore their proangiogenic function in a streptozotocin-induced diabetic mice model of CLI. GLO1 overexpression in D-ADSCs (G-D-ADSCs) was achieved using the lentivirus method. G-D-ADSCs showed a significant decrease in intracellular ROS accumulation, increase in cell viability, and resistance to apoptosis under high-glucose conditions compared with D-ADSCs. G-D-ADSCs also performed better in terms of migration, differentiation, and proangiogenic capacity than D-ADSCs in a high-glucose environment. Notably, these properties were restored to the same level as that of nondiabetic ADSCs under high-glucose conditions. G-D-ADSC transplantation induced improved reperfusion and an increased limb salvage rate compared D-ADSCs in a diabetic mice model of CLI. Histological analysis revealed higher microvessel densities and more G-D-ADSC-incorporated microvessels in the G-D-ADSC group than in the D-ADSC group, which was comparable to the nondiabetic ADSC group. Higher expression of vascular endothelial growth factor A and stromal cell-derived factor-1α and lower expression of hypoxia-induced factor-1α were also detected in the ischemic muscles from the G-D-ADSC group than that of the D-ADSC group. The results of the present study have demonstrated that protection from ROS accumulation by GLO1 overexpression is effective in reversing the impaired biological function of D-ADSCs in promoting neovascularization of diabetic CLI mice model and warrants the future clinical application of D-ADSC-based therapy in diabetic patients. Stem Cells Translational Medicine 2017;6:261-271.

KEYWORDS:

Adipose-derived stem cells; Angiogenesis; Critical limb ischemia; Diabetes; Glyoxalase-1

PMID:
28170200
PMCID:
PMC5442730
DOI:
10.5966/sctm.2015-0380
[Indexed for MEDLINE]
Free PMC Article

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