Multiple intravenous infusions of bone marrow mesenchymal stem cells reverse hyperglycemia in experimental type 2 diabetes rats

被引:106
作者
Hao, Haojie [1 ]
Liu, Jiejie [1 ]
Shen, Jing [2 ]
Zhao, Yali [1 ]
Liu, Huilin [1 ]
Hou, Qian [1 ]
Tong, Chuan [1 ]
Ti, Dongdong [1 ]
Dong, Liang [1 ]
Cheng, Yu [2 ]
Mu, Yiming [2 ]
Liu, Jianping [2 ,3 ]
Fu, Xiaobing [1 ]
Han, Weidong [1 ]
机构
[1] Chinese Peoples Liberat Army Gen Hosp, Coll Life Sci, Inst Basic Med Sci, Beijing 100853, Peoples R China
[2] Chinese Peoples Liberat Army Gen Hosp, Dept Endocrinol, Beijing 100853, Peoples R China
[3] Jiangxi Prov Peoples Hosp, Dept Endocrinol, Nanchang, Jiangxi, Peoples R China
基金
中国国家自然科学基金;
关键词
Bone marrow; Mesenchymal stem cells; Type; 2; diabetes; Multiple infusion; Hyperglycemia; INSULIN-RESISTANCE; STROMAL CELLS; MICE; INFLAMMATION; THERAPY; ISLETS; BLOOD;
D O I
10.1016/j.bbrc.2013.05.117
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The worldwide rapid increase in diabetes poses a significant challenge to current therapeutic approaches. Single-dose mesenchymal stem cell (MSC) infusion ameliorates hyperglycemia but fails to restore normoglycemia in diabetic animals. We therefore hypothesized that multiple intravenous MSC infusions may reverse hyperglycemia in type 2 diabetes (T2D) rats. We administered serial allogenous bone-marrow derived MSC infusions (1 x 10(6) cells/infusion) via the tail vein once every 2 weeks to T2D rats, induced by high-fat diet and streptozocin (STZ) administration. Hyperglycemia decreased only transiently after a single infusion in early-phase (I week) T2D rats, but approximated normal levels after at least three-time infusions. This normal blood level was maintained for at least 9 weeks. Serum concentrations of both insulin and C-peptide were dramatically increased after serial MSC infusions. Oral glucose tolerance tests revealed that glucose metabolism was significantly ameliorated. Immunofluorescence analysis of insulin/glucagon staining revealed the restoration of islet structure and number after multiple MSC treatments. When multiple-MSC treatment was initiated in late-phase (5 week) T2D rats, the results were slightly different. The results of this study suggested that a multiple-MSC infusion strategy offers a viable clinical option for T2D patients. (C) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码:418 / 423
页数:6
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