Antioxidant therapy attenuates diabetes-related impairment of bone marrow stem cells.
BACKGROUND
Bone marrow cells from humans and animals with diabetes exhibit decreased angiogenic potency, thought to be related to oxidative stress, so the present study investigated if antioxidant therapy would attenuate the diabetes-related impairment.


RESULTS
Diabetic mice were given antioxidant therapy, as a daily subcutaneous injection of superoxide dismutase-mimic (10 mg kg(-1) day(-1)). Diabetic and healthy mice given a vehicle treatment were used as the control. After 4 weeks of treatment, bone marrow mononuclear cells (BM-MNCs) were collected for analysis and the endothelial progenitor cells in BM-MNCs were evaluated by flow cytometry. The intracellular reactive oxygen species (ROS) levels in BM-MNCs were measured using 6-carboxy-2'7'-dichlorodihydrofluorescein diacetate. Endothelial differentiation from the BM-MNCs was estimated by immunostaining with VE-cadherin 7 days after culture. BM-MNCs from the control diabetic mice had fewer Flk-1/CD34 double-positive progenitor cells and higher intracellular ROS levels, with lower potency of endothelial differentiation than BM-MNCs from the healthy mice. Antioxidant therapy decreased the intracellular ROS level in BM-MNCs from that in the diabetic mice significantly (P<0.05), but increased significantly the percentage of endothelial progenitor cells (P<0.05) and their potency of differentiation into endothelial cells (P<0.05).


CONCLUSIONS
Antioxidant therapy attenuated the diabetes-related impairment of BM-MNCs by reducing oxidative stress.
Ohshima
Mako
M
Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Li
Tao-Sheng
TS
Kubo
Masayuki
M
Qin
Shu-Lan
SL
Hamano
Kimikazu
K
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D001786:Blood Glucose; D016166:Free Radical Scavengers; D008665:Metalloporphyrins; D017382:Reactive Oxygen Species; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine