在受损心脏上植入双同种异体人工程组织移植物：来自 PERISCOPE Ⅰ期临床试验的见解。

Implantation of a double allogeneic human engineered tissue graft on damaged heart: insights from the PERISCOPE phase I clinical trial.

机构信息

Heart Institute and Heart Failure Unit (iCor), Germans Trias i Pujol University Hospital (HUGTiP), Badalona, Spain; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain; ICREC Research Program, Germans Trias i Pujol Health Science Research Institute (IGTP), Spain.

Heart Institute and Heart Failure Unit (iCor), Germans Trias i Pujol University Hospital (HUGTiP), Badalona, Spain; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; ICREC Research Program, Germans Trias i Pujol Health Science Research Institute (IGTP), Spain.

出版信息

EBioMedicine. 2024 Apr;102:105060. doi: 10.1016/j.ebiom.2024.105060. Epub 2024 Mar 14.

DOI:10.1016/j.ebiom.2024.105060

PMID:38490102

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10955661/

Abstract

BACKGROUND

In preclinical studies, the use of double allogeneic grafts has shown promising results in promoting tissue revascularization, reducing infarct size, preventing adverse remodelling and fibrosis, and ultimately enhancing cardiac function. Building upon these findings, the safety of PeriCord, an engineered tissue graft consisting of a decellularised pericardial matrix and umbilical cord Wharton's jelly mesenchymal stromal cells, was evaluated in the PERISCOPE Phase I clinical trial (NCT03798353), marking its first application in human subjects.

METHODS

This was a double-blind, single-centre trial that enrolled patients with non-acute myocardial infarction eligible for surgical revascularization. Seven patients were implanted with PeriCord while five served as controls.

FINDINGS

Patients who received PeriCord showed no adverse effects during post-operative phase and one-year follow-up. No significant changes in secondary outcomes, such as quality of life or cardiac function, were found in patients who received PeriCord. However, PeriCord did modulate the kinetics of circulating monocytes involved in post-infarction myocardial repair towards non-classical inflammation-resolving macrophages, as well as levels of monocyte chemoattractants and the prognostic marker Meteorin-like in plasma following treatment.

INTERPRETATION

In summary, the PeriCord graft has exhibited a safe profile and notable immunomodulatory properties. Nevertheless, further research is required to fully unlock its potential as a platform for managing inflammatory-related pathologies.

FUNDING

This work was supported in part by grants from MICINN (SAF2017-84324-C2-1-R); Instituto de Salud Carlos III (ICI19/00039 and Red RICORS-TERAV RD21/0017/0022, and CIBER Cardiovascular CB16/11/00403) as a part of the Plan Nacional de I + D + I, and co-funded by ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER) and AGAUR (2021-SGR-01437).

摘要

背景

在临床前研究中，使用双同种异体移植物在促进组织再血管化、减少梗死面积、预防不良重构和纤维化以及最终增强心功能方面显示出良好的效果。在此基础上，评估了由去细胞心包基质和脐带华通氏胶间充质基质细胞组成的工程组织移植物 PeriCord 的安全性，该移植物已在 PERISCOPE Ⅰ期临床试验（NCT03798353）中进行了评估，这是其首次在人体中应用。

方法

这是一项双盲、单中心试验，纳入了适合手术血运重建的非急性心肌梗死患者。7 名患者植入了 PeriCord，而 5 名患者作为对照。

结果

接受 PeriCord 的患者在术后阶段和 1 年随访期间均未出现不良反应。接受 PeriCord 的患者的次要结局（如生活质量或心功能）没有显著变化。然而，PeriCord 确实调节了参与心肌梗死后修复的循环单核细胞的动力学，使其向非经典炎症消退型巨噬细胞转化，并调节了血浆中单核细胞趋化因子和预后标志物 Meteorin-like 的水平。

结论

总之，PeriCord 移植物表现出安全的特性和显著的免疫调节特性。然而，需要进一步的研究来充分挖掘其作为管理炎症相关疾病的平台的潜力。

资金

这项工作得到了 MICINN（SAF2017-84324-C2-1-R）；Instituto de Salud Carlos III（ICI19/00039 和 Red RICORS-TERAV RD21/0017/0022，以及 CIBER Cardiovascular CB16/11/00403）的部分资助，作为国家 I+D+I 计划的一部分，由 ISCIII-副局长和欧洲发展基金（FEDER）和 AGAUR（2021-SGR-01437）共同资助。