评估在羔羊体内表现出体细胞生长的工程血管移植物,以模拟缺失肺动脉分支的修复

IF 5.4 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Zeeshan H. Syedain, Matthew Lahti, Gurumurthy Hiremath, James Berry, John P. Carney, Jill Schappa Faustich, Tate Shannon, Andrea Rivera, Hadi Wiputra, Zhitian Shi, Richard Bianco, Robroy MacIver, John E. Mayer, Robert T. Tranquillo
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引用次数: 0

摘要

生长是儿科组织移植的圣杯。目前用于先天性心脏缺损手术修复的血管移植物都不具备体细胞生长能力。将供体绵羊成纤维细胞在牺牲性纤维蛋白凝胶中培育出的生物工程移植物(6 毫米)植入 3 个月大的羔羊左肺支中,时间分别为 3、6 和 18 个月。对照组为 Propaten® PTFE 移植物,植入时间为 6 个月。与 Propaten® 移植物相比,工程移植物仅在 3 个月后就出现了广泛的适当部位再细胞化,直径从植入前的 6 毫米增至 12.9 毫米,接近正常值,长度也在 6 个月时翻了一番,从 6.0 毫米增至 13.0 毫米(n = 3),这与移植物明显的体细胞生长有关(18 个月时胶原蛋白含量增加了 265%,n = 2),同时还具有良好的血液动力学特性,没有钙化。6 个月时,工程移植物的左右血流分布接近 50-50(n = 3),而 Propaten® 移植物的左右血流分布约为 20-80(n = 3),后者的直径不到 Propaten® 移植物的一半,压力梯度高出 6 倍,移植物下游的血管发育迟缓。工程移植物的直径在羔羊成年后的 12-18 个月内保持稳定(n = 2)。这项研究支持将这些具有体细胞生长能力的再生移植物用于先天性单侧肺动脉分支缺失患者的临床试验,并显示了它们改善下游肺血管发育的潜力。目前用于修复出生时心脏缺陷的血管植入物不能随儿童一起生长。这意味着,随着儿童的成长,他们需要进行多次开胸手术,用更大的植入物替换植入物。我们用捐献者的绵羊皮肤细胞培育植入物,然后将细胞从移植物中完全移除。然后,我们将移植体植入3个月大的羔羊体内。羔羊的细胞重新填充了移植体,移植体随着羔羊的成长而增大。虽然还需要进一步的实验,但我们的初步研究结果表明,在儿童身上使用类似的植入物可以提高心脏缺陷儿童的生活质量,避免他们在成长过程中需要进行多次手术来更换植入物。Syedain 等人评估了将供体绵羊成纤维细胞培育的生物工程移植物植入 3 个月大羔羊左肺支后的生长情况。移植物表现出广泛的适当部位再细胞化,直径和长度不断增加,直至羔羊成年。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Evaluation of an engineered vascular graft exhibiting somatic growth in lambs to model repair of absent pulmonary artery branch

Evaluation of an engineered vascular graft exhibiting somatic growth in lambs to model repair of absent pulmonary artery branch
Growth is the holy grail of tissue implants in pediatrics. No vascular graft currently in use for surgical repairs of congenital heart defects has somatic growth capacity. Biologically-engineered grafts (6 mm) grown from donor ovine fibroblasts in a sacrificial fibrin gel were implanted into the left pulmonary branch of 3-month old lambs for 3, 6, and 18 months. A control group of Propaten® PTFE grafts was implanted for 6 months. The engineered grafts exhibit extensive site-appropriate recellularization after only 3 months and near-normal increase of diameter from the preimplant value of 6 mm to 12.9 mm and also a doubling of length from 6.0 mm to 13.0 mm at 6 months (n = 3) associated with apparent somatic graft growth (collagen content increase of 265% over 18-month, n = 2), along with excellent hemodynamics and no calcification, in contrast to the Propaten® grafts. The left-right flow distribution is nearly 50–50 for the engineered grafts at 6 months (n = 3) compared to about 20–80 for the Propaten® grafts (n = 3), which have less than one-half the diameter, a 6-fold higher pressure gradient, and stunted vascular development downstream of the graft. The engineered grafts exhibit a stable diameter over months 12–18 when the lambs become adult sheep (n = 2). This study supports the use of these regenerative grafts with somatic growth capacity for clinical trial in patients born with a unilateral absent pulmonary artery branch, and it shows their potential for improving development of the downstream pulmonary vasculature. Blood vessel implants that are currently used to repair heart defects at birth do not grow with the child. This means that children need to have multiple open heart surgeries to replace implants with larger implants as they grow. We grew implants from a donor sheep’s skin cells, and then completely removed the cells from the graft. We then implanted the grafts in 3-month old lambs. The lambs’ cells repopulated the implants and the implants increased in size as the lambs grew. Further experiments are required first, but our preliminary findings suggest that using a similar implant in children could improve the quality of life of children with heart defects by avoiding the need for them to have multiple surgeries to replace implants as the child grows. Syedain et al. evaluate growth of biologically-engineered grafts grown from donor ovine fibroblasts in a sacrificial fibrin gel implanted into the left pulmonary branch of 3-month old lambs. The grafts exhibit extensive site-appropriate recellularization and increase in diameter and length until the lambs reach adulthood.
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