期刊
CYTOTHERAPY
卷 17, 期 1, 页码 46-57出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.jcyt.2014.06.009
关键词
CCR2; CXCR4; HIF-1 alpha; mesenchymal stromal cell migration; 17 beta-estradiol
类别
资金
- HIRG-MOHE grant of the University of Malaya [A000003-50001]
- Iran University of Medical Sciences
Background aims. Mesenchymal stromal cells (MSCs) have shown great promise for cell therapy of a wide range of diseases such as diabetes. However, insufficient viability of transplanted cells reaching to damaged tissues has limited their potential therapeutic effects. Expression of estrogen receptors on stem cells may suggest a role for 17 beta-estradiol (E2) in regulating some functions in these cells. There is evidence that E2 enhances homing of stem cells. Induction of hypoxia-inducible factor-1 alpha (HIF-1 alpha) by E2 and the profound effect of HIF-1 alpha on migration of cells have previously been demonstrated. We investigated the effect of E2 on major mediators involved in trafficking and subsequent homing of MSCs both in vitro and in vivo in diabetic rats. Methods. E2 has been selected to improve the poor migration capacity of MSCs toward sites of injury. MSCs were incubated with different concentrations of E2 for varying periods of time to investigate whether estradiol treatment could be effective to enhance the efficiency of MSC transplantation. Results. E2 significantly enhanced the viability of the cells that were blocked by ICI 182,780 (estrogen receptor antagonist). E2 also increased HIF-1 alpha, CXC chemokine receptor 4 and C-C chemokine receptor 2 protein and messenger RNA levels measured by Western blot and reverse transcription polymerase chain reaction. The enzymatic activity of matrix metalloproteinase 2 and metalloproteinase 9 was elevated in E2-treated cells through the use of gelatin zymography. Finally, the improved migration capacity of E2-treated MSCs was evaluated with the use of a Boyden chamber and in vivo migration assays. Conclusions. Our data support that conditioning of MSCs with E2 promotes migration of cells in cultured MSCs in vitro and in a diabetic rat model in vivo through regulation of major mediators of cell trafficking.
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