Treatment of Myocardial Infarction with Gene-modified Mesenchymal Stem Cells in a Small Molecular Hydrogel.
Treatment of Myocardial Infarction with Gene-modified Mesenchymal Stem Cells in a Small Molecular Hydrogel.
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用小分子水凝胶中的基因修饰间充质干细胞治疗心肌梗死
DOI：
10.1038/s41598-017-15870-z
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发表时间：
2017-11-20
影响因子：
4.6
通讯作者：
Ou C
中科院分区：
文献类型：
--
作者：
Wu Z;Chen G;Zhang J;Hua Y;Li J;Liu B;Huang A;Li H;Chen M;Ou C
心肌梗死时细胞外微环境可降低移植大鼠间充质干细胞（MSCs）的作用。我们测试了一种新型的小分子水凝胶（SMH）是否可以为肝细胞生长因子（HGF）修饰的MSC提供支架，并在MI后保护心脏功能的同时减轻心室重构。在体外，HGF过表达的MSCs对缺氧的反应中Bcl-2的表达增加，Bax和caspase-3的表达减少。免疫细胞化学结果显示，5-氮胞苷（5-aza）联合SMH组心肌肌钙蛋白（cTnT）、结蛋白（desmin）和连接蛋白43（connexin 43）表达较5-aza单独组明显增强。生物发光成像表明，当用SMH注射腺病毒（ad-HGF）转染的MSC时，移植细胞的保留和存活最高。超声心动图和组织学检查证实Ad-HGF-SMHs-MSCs组的心脏功能和结构改善优于其他组。我们的研究表明：HGF可减轻细胞凋亡，促进MSC生长。SMHs可改善MSC移植后的干细胞粘附、存活和心肌细胞分化。SMHs联合修饰的MSCs可明显减少瘢痕面积，改善心功能。
The effect of transplanted rat mesenchymal stem cells (MSCs) can be reduced by extracellular microenvironment in myocardial infarction (MI). We tested a novel small-molecular hydrogel (SMH) on whether it could provide a scaffold for hepatocyte growth factor (HGF)-modified MSCs and alleviate ventricular remodeling while preserving cardiac function after MI. Overexpression of HGF in MSCs increased Bcl-2 and reduced Bax and caspase-3 levels in response to hypoxiain vitro. Immunocytochemistry demonstrated that cardiac troponin (cTnT), desmin and connexin 43 expression were significantly enhanced in the 5-azacytidine (5-aza) with SMH group compared with the 5-aza only groupin vitroandin vivo. Bioluminescent imaging indicated that retention and survival of transplanted cells was highest when MSCs transfected with adenovirus (ad-HGF) were injected with SMH. Heart function and structure improvement were confirmed by echocardiography and histology in the Ad-HGF-SMHs-MSCs group compared to other groups. Our study showed that: HGF alleviated cell apoptosis and promoted MSC growth. SMHs improved stem cell adhesion, survival and myocardial cell differentiation after MSC transplantation. SMHs combined with modified MSCs significantly decreased the scar area and improved cardiac function.
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影响因子：
120.7
作者：
Heldman, Alan W.;DiFede, Darcy L.;Fishman, Joel E.;Zambrano, Juan P.;Trachtenberg, Barry H.;Karantalis, Vasileios;Mushtaq, Muzammil;Williams, Adam R.;Suncion, Viky Y.;McNiece, Ian K.;Ghersin, Eduard;Soto, Victor;Lopera, Gustavo;Miki, Roberto;Willens, Howard;Hendel, Robert;Mitrani, Raul;Pattany, Pradip;Feigenbaum, Gary;Oskouei, Behzad;Byrnes, John;Lowery, Maureen H.;Sierra, Julio;Pujol, Mariesty V.;Delgado, Cindy;Gonzalez, Phillip J.;Rodriguez, Jose E.;Bagno, Luiza Lima;Rouy, Didier;Altman, Peter;Foo, Cheryl Wong Po;da Silva, Jose;Anderson, Erica;Schwarz, Richard;Mendizabal, Adam;Hare, Joshua M.
通讯作者：
Hare, Joshua M.
影响因子：
46.9
作者：
Lane, Steven W.;Williams, David A.;Watt, Fiona M.
通讯作者：
Watt, Fiona M.
影响因子：
4.6
作者：
Dong LH;Jiang YY;Liu YJ;Cui S;Xia CC;Qu C;Jiang X;Qu YQ;Chang PY;Liu F
通讯作者：
Liu F
影响因子：
5.1
作者：
Gao, Feng;Hu, Xin-yang;Wang, Jian-an
通讯作者：
Wang, Jian-an
胚胎干细胞与温度响应型壳聚糖水凝胶共注射改善梗塞心脏功能
影响因子：
4.1
作者：
Lu, Wen-Ning;Lue, Shuang-Hong;Wang, Chang-Yong
通讯作者：
Wang, Chang-Yong