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小儿先天性心脏病手术中脱细胞猪小肠黏膜下层细胞外基质(CorMatrix)的组织学检查

Histologic examination of decellularized porcine intestinal submucosa extracellular matrix (CorMatrix) in pediatric congenital heart surgery.

作者信息

Woo Jennifer S, Fishbein Michael C, Reemtsen Brian

机构信息

Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, 10833 Le Conte Avenue, CHS 13-145, Los Angeles, CA, United States.

Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, 10833 Le Conte Avenue, CHS 13-145, Los Angeles, CA, United States.

出版信息

Cardiovasc Pathol. 2016 Jan-Feb;25(1):12-7. doi: 10.1016/j.carpath.2015.08.007. Epub 2015 Aug 28.

DOI:10.1016/j.carpath.2015.08.007
PMID:26453090
Abstract

BACKGROUND

CorMatrix is a decellularized porcine small intestinal submucosa extracellular matrix that has gained attention as a promising alternative to current materials used in cardiac repair. While animal models demonstrate integration of CorMatrix material with host tissue, the histologic characteristics of CorMatrix used in humans are less well-characterized. In this retrospective study, we report our experience with CorMatrix material used in pediatric congenital heart surgery and describe the histology of CorMatrix material and of surrounding native tissue in explanted specimens.

METHODS

Records were reviewed of all pediatric patients implanted with CorMatrix from a single institution (2011-2014). Histologic examinations were performed on CorMatrix and other tissues removed. Explanted samples of CorMatrix and adherent tissues were evaluated for inflammation (acute and chronic), fibrosis, necrosis, degenerative changes, eosinophil response, foreign-body giant cell reaction, neovascularization, and calcification of tissues on a semiquantitative basis (0, none; 1, mild; 2, moderate; 3, marked). Presence of degeneration within CorMatrix and necrosis of surrounding tissue were noted.

RESULTS

CorMatrix was utilized in 532 pediatric heart reconstruction procedures since 2011. Twelve explanted CorMatrix specimens from 11 pediatric patients including 4 valves (2 mitral and 2 aortic) and 8 outflow/septal/conduit patches were identified and evaluated. Six cases (5 patients) demonstrated clinical evidence of graft failure prior to surgery (n=6, 1%). Chronic inflammation was seen in adjacent native tissue in 11/12 cases and consisted predominantly of a mixed population of lymphocytes, macrophages, and plasma cells. Acute inflammation was seen in three cases (3/12). Fibrosis of the surrounding native tissue was seen in all CorMatrix specimens. Eosinophils were present in 6/12 cases. Calcification in surrounding tissue was present in 3/12 cases. Giant cell reaction in adjacent native tissue was seen in 8/12 cases. Neovascularization was seen in surrounding native tissue in 5/12 cases. Degeneration of CorMatrix material was seen in 9/12 cases. Necrosis of surrounding tissue was also identified in 5/12 cases. CorMatrix was not resorbed and no cases demonstrated any remodeling of CorMatrix material by integration of native mesenchymal cells or myocytes.

CONCLUSION

CorMatrix may be associated with a marked inflammatory response, including a foreign-body giant cell reaction and fibrosis of the surrounding native tissue. Degenerative changes of CorMatrix material are also seen in a majority of explanted specimens. No histologic differences were seen between patients with clinical evidence of graft failure versus patients requiring graft removal due to other factors. Additionally, no cases showed evidence of tissue integration or recellularization of patch material. Our overall clinical experience with CorMatrix demonstrates a favorable outcome for pediatric patients undergoing cardiac reconstructive surgery. However, there is no histologic evidence that CorMatrix acts as a scaffold for reconstitution of the native cardiovascular structures.

摘要

背景

CorMatrix是一种脱细胞猪小肠黏膜下层细胞外基质,作为心脏修复中当前所用材料的一种有前景的替代品而受到关注。虽然动物模型显示CorMatrix材料与宿主组织整合,但用于人类的CorMatrix的组织学特征尚未得到充分描述。在这项回顾性研究中,我们报告了在小儿先天性心脏手术中使用CorMatrix材料的经验,并描述了CorMatrix材料及外植标本中周围天然组织的组织学情况。

方法

回顾了来自单一机构(2011 - 2014年)所有植入CorMatrix的小儿患者的记录。对取出的CorMatrix和其他组织进行组织学检查。对外植的CorMatrix样本及附着组织进行炎症(急性和慢性)、纤维化、坏死、退行性改变、嗜酸性粒细胞反应、异物巨细胞反应、新生血管形成和组织钙化的半定量评估(0,无;1,轻度;2,中度;3,重度)。记录CorMatrix内的变性情况及周围组织的坏死情况。

结果

自2011年以来,CorMatrix用于532例小儿心脏重建手术。从11例小儿患者中识别并评估了12个外植CorMatrix标本,包括4个瓣膜(2个二尖瓣和2个主动脉瓣)和8个流出道/间隔/管道补片。6例(5名患者)在手术前有移植失败的临床证据(n = 6,1%)。11/12例在相邻天然组织中可见慢性炎症,主要由淋巴细胞、巨噬细胞和浆细胞混合组成。3例(3/12)可见急性炎症。所有CorMatrix标本中均可见周围天然组织的纤维化。6/12例中有嗜酸性粒细胞。3/12例周围组织中有钙化。8/12例在相邻天然组织中可见巨细胞反应。5/12例周围天然组织中有新生血管形成。9/12例可见CorMatrix材料变性。5/12例也发现周围组织坏死。CorMatrix未被吸收,且没有病例显示天然间充质细胞或心肌细胞整合对CorMatrix材料进行任何重塑。

结论

CorMatrix可能与明显的炎症反应相关,包括异物巨细胞反应和周围天然组织的纤维化。在大多数外植标本中也可见CorMatrix材料的退行性改变。有移植失败临床证据的患者与因其他因素需要移除移植物的患者之间在组织学上没有差异。此外,没有病例显示补片材料有组织整合或再细胞化的证据。我们使用CorMatrix的总体临床经验表明,接受心脏重建手术的小儿患者预后良好。然而,没有组织学证据表明CorMatrix可作为天然心血管结构重建的支架。

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