Delivery of progenitor cells with injectable shear-thinning hydrogel maintains geometry and normalizes strain to stabilize cardiac function after ischemia.
Delivery of progenitor cells with injectable shear-thinning hydrogel maintains geometry and normalizes strain to stabilize cardiac function after ischemia.
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DOI：
10.1016/j.jtcvs.2018.07.117
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发表时间：
2019-04
期刊：
影响因子：
--
通讯作者：
Atluri P
中科院分区：
文献类型：
--
作者：
Gaffey AC;Chen MH;Trubelja A;Venkataraman CM;Chen CW;Chung JJ;Schultz S;Sehgal CM;Burdick JA;Atluri P
心肌梗死后，心室会发生不利的重塑，导致生物力学异常和功能下降。我们假设，组织工程治疗可以通过机械应力的减少和由于改善内皮祖细胞的保留和透明质酸剪切稀释胶的内在生物力学特性而保留拉伸心肌特性来最小化缺血后的重构。取成年Wistar大鼠内皮祖细胞，悬浮于剪切稀释胶中。在急性心肌梗死模型中，将构建物注射到缺血大鼠心肌交界区。分析对照组(磷酸盐缓冲液)、内皮祖细胞、剪切变薄凝胶和剪切变薄凝胶+内皮祖细胞的心肌重构、拉伸特性和血流动力学功能。新型高分辨率、高灵敏度的超声波，具有斑点跟踪功能，可用于全局应变分析。单轴测试评估了拉伸生物力学特性。与单独注射内皮祖细胞相比，剪切稀释胶+内皮祖细胞注射显著增加了内皮祖细胞在心肌内的植入和保留。使用应变超声心动图，剪切稀释凝胶+内皮祖细胞组的左心室射血分数显著改善(69.5%±10.8%比40.1%±4.6%，P=0.04)。与对照组相比，剪切性稀释胶+内皮祖细胞治疗组心肌纵向位移明显正常化，心肌运动速度趋于稳定(0.84±0.3 cm/S vs 0.11±0.01 cm/S，P=0.03)。剪切稀释胶+内皮祖细胞组心肌应变(4.5%±0.45%)显著高于剪切稀释胶(3.7%±0.24%)、内皮祖细胞(3.5%±0.97%)和对照组(8.6%±0.3%，P=0.05)。在剪切稀释凝胶+内皮祖细胞队列中注意到动态硬度的结果降低。这种新型的可注射剪切稀释型透明质酸水凝胶显示了交界区心肌的稳定，减少了不利的心肌重构，并保存了心肌生物力学。该细胞结构提供了应变测量的标准化，并减少了左心室的扩张，从而导致左心室功能的改善。
The ventricle undergoes adverse remodeling after myocardial infarction, resulting in abnormal biomechanics and decreased function. We hypothesize that tissue-engineered therapy could minimize postischemic remodeling through mechanical stress reduction and retention of tensile myocardial properties due to improved endothelial progenitor cell retention and intrinsic biomechanical properties of the hyaluronic acid shear-thinning gel. Endothelial progenitor cells were harvested from adult Wistar rats and resuspended in shear-thinning gel. The constructs were injected at the border zone of ischemic rat myocardium in an acute model of myocardial infarction. Myocardial remodeling, tensile properties, and hemodynamic function were analyzed: control (phosphate-buffered saline), endothelial progenitor cells, shear-thinning gel, and shear-thinning gel + endothelial progenitor cells. Novel high-resolution, high-sensitivity ultrasound with speckle tracking allowed for global strain analysis. Uniaxial testing assessed tensile biomechanical properties. Shear-thinning gel + endothelial progenitor cell injection significantly increased engraftment and retention of the endothelial progenitor cells within the myocardium compared with endothelial progenitor cells alone. With the use of strain echocardiography, a significant improvement in left ventricular ejection fraction was noted in the shear-thinning gel + endothelial progenitor cell cohort compared with control (69.5% ± 10.8% vs 40.1% ± 4.6%, P = .04). A significant normalization of myocardial longitudinal displacement with subsequent stabilization of myocardial velocity with shear-thinning gel + endothelial progenitor cell therapy compared with control was also evident (0.84 + 0.3 cm/s vs 0.11 ± 0.01 cm/s, P = .03). A significantly positive and higher myocardial strain was observed in shear-thinning gel + endothelial progenitor cell (4.5% ± 0.45%) compared with shear-thinning gel (3.7% ± 0.24%), endothelial progenitor cell (3.5% ± 0.97%), and control (8.6% ± 0.3%, P = .05). A resultant reduction in dynamic stiffness was noted in the shear-thinning gel + endothelial progenitor cell cohort. This novel injectable shear-thinning hyaluronic acid hydrogel demonstrates stabilization of border zone myocardium with reduction in adverse myocardial remodeling and preservation of myocardial biomechanics. The cellular construct provides a normalization of strain measurements and reduces left ventricular dilatation, thus resulting in improvement of left ventricular function.
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DOI：
10.1016/j.jtcvs.2014.06.038
发表时间：
2014-09
期刊：
The Journal of thoracic and cardiovascular surgery
影响因子：
--
作者：
Atluri P;Miller JS;Emery RJ;Hung G;Trubelja A;Cohen JE;Lloyd K;Han J;Gaffey AC;MacArthur JW;Chen CS;Woo YJ
通讯作者：
Woo YJ
影响因子：
37.8
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Hofmann, M;Wollert, KC;Drexler, H
通讯作者：
Drexler, H
影响因子：
2
作者：
Cottrell, Caroline;Kirkpatrick, James N
通讯作者：
Kirkpatrick, James N
影响因子：
20.1
作者：
Bauer M;Cheng S;Jain M;Ngoy S;Theodoropoulos C;Trujillo A;Lin FC;Liao R
通讯作者：
Liao R
DOI：
10.1016/j.jtcvs.2015.07.035
发表时间：
2015-11
期刊：
The Journal of thoracic and cardiovascular surgery
影响因子：
--
作者：
Gaffey AC;Chen MH;Venkataraman CM;Trubelja A;Rodell CB;Dinh PV;Hung G;MacArthur JW;Soopan RV;Burdick JA;Atluri P
通讯作者：
Atluri P