A fusion protein of hepatocyte growth factor enhances reconstruction of myocardium in a cardiac patch derived from porcine urinary bladder matrix.

A fusion protein of hepatocyte growth factor enhances reconstruction of myocardium in a cardiac patch derived from porcine urinary bladder matrix.
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DOI:
10.1016/j.jtcvs.2008.07.008
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发表时间:
2008-11
影响因子:
6
通讯作者:
Zenati, Marco A.
Zenati, Marco A.
中科院分区:
医学1区
文献类型:
--
作者:
Ota, Takeyoshi;Gilbert, Thomas W.;Schwartzman, David;McTiernan, Charles F.;Kitajima, Takashi;Ito, Yoshihiro;Sawa, Yoshiki;Badylak, Stephen F.;Zenati, Marco A.

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我们试图在猪模型中使用膀胱基质(UBM)结合肝细胞生长因子(HGF)和纤维连接蛋白胶原结合结构域(CBD)的融合蛋白来促进心肌修复。CBD作为中介促进HGF结合,增强HGF在UBM内的稳定性。将合并CBD-HGF的UBM植入猪右心室壁(f组)以修复手术造成的缺损。未处理UBM贴片(u组)和涤纶贴片(d组)作为对照组(N=5/组)。术后60天进行机电测绘。线性局部缩短(LLS)用于评估区域收缩性,并记录电活动。F组LLS较对照组明显改善(F:0.51±1.57%*,U: - 1.06±1.84%,D: - 2.72±2.59%,*p<0.05),但低于正常心肌(13.7±4.3%)*。F组平均电活动为1.49±0.82mV,显著高于对照组(U:0.93±0.71mV; D:0.30±0.22mV)*,显著低于正常心肌(8.24±2.49mV)*。组织学检查以α-平滑肌肌动蛋白阳性细胞为主,F组细胞层最厚,D组细胞层最薄,有心内膜内皮单层。α-肌动蛋白阳性细胞的分散孤立岛仅在F组中观察到,而在对照组中没有,提示心肌细胞的存在。与单独的UBM或涤纶相比,CBD-HGF-UBM贴片显示出更高的收缩性和电活动,并促进了宿主细胞的均匀再生。合并CBD-HGF的UBM可能有助于心肌重构。
We sought to promote myocardial repair using urinary bladder matrix (UBM) incorporated with a fusion protein which combined hepatocyte growth factor (HGF) and fibronectin collagen-binding-domain (CBD) in a porcine model. CBD acted as an intermediary to promote HGF binding and enhance HGF stability within UBM. UBM incorporated with CBD-HGF was implanted into the porcine right ventricular wall (F-group) to repair a surgically created defect. Untreated UBM patches (U-group) and Dacron patches (D-group) served as controls (N=5/group). Electromechanical mapping was performed at 60-days after surgery. Linear local shortening (LLS) was used to assess regional contractility, and electrical activity was recorded. The LLS was significantly improved in the F group compared with controls (F:0.51 ± 1.57%*, U:− 1.06 ± 1.84%, D: −2.72 ± 2.59%; *p<0.05), while they were inferior to the normal myocardium(13.7 ± 4.3%)*. Mean electrical activity was 1.49±0.82mV in the F group, which was statistically greater than control groups (U:0.93 ± 0.71mV; D:0.30 ± 0.22mV)* and less than the normal myocardium (8.24±2.49mV)*. Histological examination showed predominant α-smooth muscle actin positive cells with the F group showing the thickest layer and the D group the thinnest layer, with an endocardial endothelial monolayer. Scattered isolated islands of α-actinin positive cells were observed only in the F group, but not in the controls, suggesting the presence of cardiomyocytes. The CBD-HGF-UBM patch demonstrated increased contractility and electrical activity compared to UBM alone or Dacron, and facilitated a homogeneous repopulation of host cells. UBM incorporated with CBD-HGF may contribute to constructive myocardial remodeling.
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