Nitric oxide releasing hydrogel enhances the therapeutic efficacy of mesenchymal stem cells for myocardial infarction

被引：128

作者：

Yao, Xinpeng ^{[1
]}

Liu, Yi ^{[2
]}

Gao, Jie ^{[1
]}

Yang, Liang ^{[3
]}

Mao, Duo ^{[1
]}

Stefanitsch, Christina ^{[4
]}

Li, Yang ^{[3
]}

Zhang, Jun ^{[1
]}

Ou, Lailiang ^{[1
]}

Kong, Deling ^{[1
]}

Zhao, Qiang ^{[1
]}

Li, Zongjin ^{[3
]}

机构：

[1] Nankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, Minist Educ,Key Lab Bioact Mat, Tianjin 300071, Peoples R China

[2] Tianjin Med Univ, Sch Basic Med, Dept Biol, Tianjin 300070, Peoples R China

[3] Nankai Univ, Sch Med, Tianjin 300071, Peoples R China

[4] Danube Univ Krems, Dept Hlth Sci & Biomed, A-3500 Krems, Austria

来源：

BIOMATERIALS | 2015年 / 60卷

基金：

中国国家自然科学基金;

关键词：

Hydrogel; Nitric oxide; Adipose-derived mesenchymal stem cells (AD-MSCs); Myocardial infarction; Molecular imaging; Angiogenesis; CHITOSAN HYDROGEL; S-NITROSYLATION; SURVIVAL; CARDIOMYOCYTES; REGENERATION; ENGRAFTMENT; DELIVERY; TRANSPLANTATION; BIOMATERIALS; INJECTION;

D O I：

10.1016/j.biomaterials.2015.04.046

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Stem cell therapy has been proved to be an effective approach to ameliorate the heart remodeling post myocardial infarction (MI). However, poor cell engraftment and survival in ischemic myocardium limits the successful use of cellular therapy for treating MI. Here, we sought to transplant adipose derived-mesenchymal stem cells (AD-MSCs) with a hydrogel (NapFF-NO), naphthalene covalently conjugated a short peptide, FFGGG, and beta-galactose caged nitric oxide (NO) donor, which can release NO molecule in response to beta-galactosidase. AD-MSCs, either from transgenic mice that constitutively express GFP and firefly luciferase (Fluc), or express Fluc under the control of VEGFR2 promoter, were co-transplanted with NapFF-NO hydrogel into murine MI models. Improved cell survival and enhanced cardiac function were confirmed by bioluminescence imaging (BLI) and echocardiogram respectively. Moreover, increasing VEGFR2-luc expression was also tracked in real-time in vivo, indicating NapFF-NO hydrogel stimulated VEGF secretion of AD-MSCs. To investigate the therapeutic mechanism of NapFF-NO hydrogel, cell migration assay, paracrine action of AD-MSCs, and histology analysis were carried out. Our results revealed that condition medium from AD-MSCs cultured with NapFF-NO hydrogel could promote endothelial cell migration. Additionally, AD-MSCs showed significant improvement secretion of angiogenic factors VEGF and SDF-1 alpha in the presence of NapFF-NO hydrogel. Finally, postmortem analysis confirmed that transplanted AD-MSCs with NapFF-NO hydrogel could ameliorate heart function by promoting angiogenesis and attenuating ventricular remodeling. In conclusion, NapFF-NO hydrogel can obviously improve therapeutic efficacy of AD-MSCs for MI by increasing cell engraftment and angiogenic paracrine action. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：130 / 140

页数：11

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