细胞外无细胞同种异体心脏瓣膜体内再细胞化的早期观察。

Early Insight Into In Vivo Recellularization of Cell-Free Allogenic Heart Valves.

机构信息

Department for Cardiothoracic, Transplant, and Vascular Surgery, Hannover Medical School, Hannover, Germany.

Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Hannover, Germany.

出版信息

Ann Thorac Surg. 2019 Aug;108(2):581-589. doi: 10.1016/j.athoracsur.2019.02.058. Epub 2019 Mar 28.

DOI:10.1016/j.athoracsur.2019.02.058

PMID:30928547

Abstract

BACKGROUND

Unlike the vast amount of animal data available on the recellularization of allogenic decellularized heart valves (DHVs), there have only been sporadic histologic reports on such grafts in humans.

METHODS

Two experienced cardiac pathologists independently evaluated human specimens obtained during reoperation between December 2010 and April 2017 DHVs in seven categories after automated staining (scores: 0 to 6) in comparison with published data. An optimal result of 42 points was classified as 100%.

RESULTS

We found that 364 DHVs, 236 decellularized pulmonary homografts (DPHs), and 128 decellularized aortic homografts (DAHs) were implanted, and freedom from explantation was 96.1% (DAH) and 98.7% (DPH). Reoperations were because of (suspected) endocarditis in 5 of 11 patients, stenosis at the subvalvular or valvular or supravalvular level in 3 of 11 patients, planned staged reoperation in 2 of 11 patients, and 1 heart transplantation. Good reader agreement was reflected by an interagreement weighted κ of 0.783 (95% confidence interval: 0.707 to 0.859). The relative histologic score in nonendocarditis specimens was 76% ± 4.3% (maximum 81%). Intracellular procollagen type 1 production was found in recipient mesenchymal cells within the transplanted grafts. In endocarditis specimens the histologic score was significantly lower with 48% ± 7.3% (minimum 41%, p = 0.0004) because of leucocyte infiltration and matrix degradation. One DPH showed immune system-mediated graft failure. Grafts obtained during the first 12 months after implantation were not evenly repopulated with less recellularization in the inner parts; no difference was found between DAH and DPH with respect to extent of recellularization.

CONCLUSIONS

Substantial in vivo recellularization with noninflammatory cells was observed in this study. Spontaneous recellularization appears to require multiple months, which correspondingly has an impact on size selection for growing patients.

摘要

背景

与大量关于同种异体去细胞心脏瓣膜（DHV）再细胞化的动物数据相比，仅有少数关于此类移植物在人类中的组织学报告。

方法

两名经验丰富的心脏病理学家分别对 2010 年 12 月至 2017 年 4 月间再次手术获得的人类标本进行评估，共涉及 364 个 DHV，236 个去细胞化肺动脉同种移植物（DPH）和 128 个去细胞化主动脉同种移植物（DAH），评估内容包括自动染色后的 7 个类别（评分：0 至 6），并与已发表的数据进行比较。将 42 分的最佳结果定义为 100%。

结果

我们发现，11 例患者中有 5 例因（疑似）心内膜炎、3 例因瓣下、瓣上或瓣部狭窄、2 例因计划分期再次手术和 1 例因心脏移植而进行了再次手术。11 例患者中有 11 例患者中植入了 364 个 DHV、236 个去细胞化肺动脉同种移植物（DPH）和 128 个去细胞化主动脉同种移植物（DAH），移植物的无再取出率为 96.1%（DAH）和 98.7%（DPH）。良好的读者间一致性反映在组内一致性加权κ值为 0.783（95%置信区间：0.707 至 0.859）。非心内膜炎标本的相对组织学评分（组织学评分的最大值为 81%）为 76%±4.3%。在植入的移植物中，受体间质细胞内可见细胞内原胶原蛋白 1 型的产生。在心内膜炎标本中，由于白细胞浸润和基质降解，组织学评分显著较低，为 48%±7.3%（最低 41%，p=0.0004）。一个 DPH 显示免疫系统介导的移植物失败。在植入后的头 12 个月内获得的移植物并未均匀地再细胞化，内部再细胞化程度较低；在 DAH 和 DPH 之间，再细胞化程度没有差异。