Angiogenic and Restorative Abilities of Human Mesenchymal Stem Cells Were Reduced Following Treatment With Serum From Diabetes Mellitus Type 2 Patients

被引:46
作者
Rezaie, Jafar [1 ]
Mehranjani, Malek S. [1 ]
Rahbarghazi, Reza [2 ,3 ]
Shariatzadeh, Mohammad A. [1 ]
机构
[1] Arak Univ, Fac Sci, Dept Biol, POB 38156-8-8349, Arak, Iran
[2] Tabriz Univ Med Sci, Stem Cell Res Ctr, Tabriz, Iran
[3] Tabriz Univ Med Sci, Fac Adv Med Sci, Dept Appl Cell Sci, Tabriz, Iran
关键词
HUMAN MESENCHYMAL STEM CELLS; DIABETES MELLITUS TYPE 2; DIFFERENTIATION AND PARACRINE ANGIOGENESIS PROPERTIES; RESTORATIVE ABILITY; ENDOTHELIAL PROGENITOR CELLS; HIGH GLUCOSE; VEGF EXPRESSION; STROMAL CELLS; TRANSPLANTATION;
D O I
10.1002/jcb.26211
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
This experiment investigated the impact of serum from patients with type 2 diabetes mellitus on the angiogenic behavior of human mesenchymal stem cells in vitro. Changes in the level of Ang-1, Ang-2, cell migration, and trans-differentiation into pericytes and endothelial lineage were monitored after 7 days. The interaction of mesenchymal stem cells with endothelial cells were evaluated using surface plasmon resonance technique. Paracrine restorative effect of diabetic stem cells was tested on pancreatic cells. Compared to data from FBS and normal serum, diabetic serum reduced the stem cell survival and chemotaxis toward VEGF and SDF-1 (P<0.05). Diabetic condition were found to decline cell migration rate and the activity of MMP-2 and -9 (P<0.05). The down-regulation of VEGFR-2 and CXCR-4 was observed with an increase in the level of miR-1-3p and miR-15b-5p at the same time. The paracrine angiogenic potential of diabetic stem cells was disturbed via the changes in the dynamic of Ang-1, Ang-2, and VEGF. Surface plasmon resonance analysis showed that diabetes could induce an aberrant increase in the interaction of stem cells with endothelial cells. After treatment with diabetic serum, the expression of VE-cadherin and NG2 and ability for uptake of Dil-Ac-LDL were reduced (P<0.01). Conditioned media prepared from diabetic stem cells were unable to decrease fatty acid accumulation in -cells (P<0.05). The level of insulin secreted by -cells was not affected after exposure to supernatant from diabetic or non-diabetic mesenchymal stem cells. Data suggest diabetes could decrease angiogenic and restorative effect of stem cells in vitro. J. Cell. Biochem. 119: 524-535, 2018. (c) 2017 Wiley Periodicals, Inc.
引用
收藏
页码:524 / 535
页数:12
相关论文
共 37 条
[1]   Chemokines in proliferative diabetic retinopathy and proliferative vitreoretinopathy [J].
Abu El-Asrar, Ahmed M. ;
Struyf, Sofie ;
Kangave, Dustan ;
Geboes, Karel ;
Van Damme, Jo .
EUROPEAN CYTOKINE NETWORK, 2006, 17 (03) :155-165
[2]   Effects of matrix metalloproteinases on the fate of mesenchymal stem cells [J].
Almalki, Sami G. ;
Agrawal, Devendra K. .
STEM CELL RESEARCH & THERAPY, 2016, 7
[3]   Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system [J].
Augustin, Hellmut G. ;
Koh, Gou Young ;
Thurston, Gavin ;
Alitalo, Kari .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2009, 10 (03) :165-177
[4]   Mesenchymal Stem Cells Improve Healing of Diabetic Foot Ulcer [J].
Cao, Yue ;
Gang, Xiaokun ;
Sun, Chenglin ;
Wang, Guixia .
JOURNAL OF DIABETES RESEARCH, 2017, 2017
[5]   Paracrine Factors of Mesenchymal Stem Cells Recruit Macrophages and Endothelial Lineage Cells and Enhance Wound Healing [J].
Chen, Liwen ;
Tredget, Edward E. ;
Wu, Philip Y. G. ;
Wu, Yaojiong .
PLOS ONE, 2008, 3 (04)
[6]   Advanced glycation end products impair function of late endothelial progenitor cells through effects on protein kinase Akt and cyclooxygenase-2 [J].
Chen, Qin ;
Dong, Li ;
Wang, Lian ;
Kang, Lina ;
Xu, Biao .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2009, 381 (02) :192-197
[7]   Targeted migration of mesenchymal stem cells modified with CXCR4 gene to infarcted myocardium improves cardiac performance [J].
Cheng, Zhaokang ;
Ou, Lailiang ;
Zhou, Xin ;
Li, Fei ;
Jia, Xiaohua ;
Zhang, Yinguo ;
Liu, Xiaolei ;
Li, Yuming ;
Ward, Christopher A. ;
Melo, Luis G. ;
Kong, Deling .
MOLECULAR THERAPY, 2008, 16 (03) :571-579
[8]   Decreased cardiac expression of vascular endothelial growth factor and its receptors in insulin-resistant and diabetic states - A possible explanation for impaired collateral formation in cardiac tissue [J].
Chou, E ;
Suzuma, I ;
Way, KJ ;
Opland, D ;
Clermont, AC ;
Naruse, K ;
Suzuma, K ;
Bowling, NL ;
Vlahos, CJ ;
Aiello, LP ;
King, GL .
CIRCULATION, 2002, 105 (03) :373-379
[9]   Effect of high glucose on extensive culturing of mesenchymal stem cells derived from subcutaneous fat, omentum fat and bone marrow [J].
Dhanasekaran, M. ;
Indumathi, S. ;
Rajkumar, J. S. ;
Sudarsanam, D. .
CELL BIOCHEMISTRY AND FUNCTION, 2013, 31 (01) :20-29
[10]   Glycaemic control improves perfusion recovery and VEGFR2 protein expression in diabetic mice following experimental PAD [J].
Dokun, Ayotunde O. ;
Chen, Lingdan ;
Lanjewar, Swapnil S. ;
Lye, Robert John ;
Annex, Brian H. .
CARDIOVASCULAR RESEARCH, 2014, 101 (03) :364-372