首例人类心包心脏生物植入物：同种异体工程组织移植物的可扩展性和 GMP 制造。
First-in-human PeriCord cardiac bioimplant: Scalability and GMP manufacturing of an allogeneic engineered tissue graft.
机构信息
ICREC Research Program, Germans Trias i Pujol Health Science Research Institute, Can Ruti Campus, Badalona, Spain; Heart Institute (iCor), Germans Trias i Pujol University Hospital, Carretera de Canyet s/n, 08916 Badalona, Spain; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Institut d'Investigació Biomèdica de Bellvitge - IDIBELL, L'Hospitalet de Llobregat, Spain.
Cell Therapy Service, Banc de Sang i Teixits, Edifici Dr. Frederic Duran i Jordà, Passeig Taulat, 116, 08005 Barcelona, Spain.
出版信息
EBioMedicine. 2020 Apr;54:102729. doi: 10.1016/j.ebiom.2020.102729. Epub 2020 Apr 15.
BACKGROUND
Small cardiac tissue engineering constructs show promise for limiting post-infarct sequelae in animal models. This study sought to scale-up a 2-cm preclinical construct into a human-size advanced therapy medicinal product (ATMP; PeriCord), and to test it in a first-in-human implantation.
METHODS
The PeriCord is a clinical-size (12-16 cm) decellularised pericardial matrix colonised with human viable Wharton's jelly-derived mesenchymal stromal cells (WJ-MSCs). WJ-MSCs expanded following good manufacturing practices (GMP) met safety and quality standards regarding the number of cumulative population doublings, genomic stability, and sterility. Human decellularised pericardial scaffolds were tested for DNA content, matrix stiffness, pore size, and absence of microbiological growth.
FINDINGS
PeriCord implantation was surgically performed on a large non-revascularisable scar in the inferior wall of a 63-year-old male patient. Coronary artery bypass grafting was concomitantly performed in the non-infarcted area. At implantation, the 16-cm pericardial scaffold contained 12·5 × 10 viable WJ-MSCs (85·4% cell viability; <0·51 endotoxin units (EU)/mL). Intraoperative PeriCord delivery was expeditious, and secured with surgical glue. The post-operative course showed non-adverse reaction to the PeriCord, without requiring host immunosuppression. The three-month clinical follow-up was uneventful, and three-month cardiac magnetic resonance imaging showed ~9% reduction in scar mass in the treated area.
INTERPRETATION
This preliminary report describes the development of a scalable clinical-size allogeneic PeriCord cardiac bioimplant, and its first-in-human implantation.
FUNDING
La Marató de TV3 Foundation, Government of Catalonia, Catalan Society of Cardiology, "La Caixa" Banking Foundation, Spanish Ministry of Science, Innovation and Universities, Institute of Health Carlos III, and the European Regional Development Fund.
背景
小型心脏组织工程构建体在动物模型中显示出限制梗死后后遗症的潜力。本研究旨在将 2cm 的临床前构建体放大为人类大小的先进治疗药物产品（ATMP；PeriCord），并在首次人体植入中进行测试。
方法
PeriCord 是一种临床大小（12-16cm）脱细胞心包基质，其中定植有人类活 Wharton 胶衍生间充质基质细胞（WJ-MSCs）。WJ-MSCs 按照良好生产规范（GMP）进行扩增，符合安全性和质量标准，包括累积倍增次数、基因组稳定性和无菌性。对人类脱细胞心包支架进行了 DNA 含量、基质硬度、孔径和无微生物生长的测试。
结果
在一名 63 岁男性患者下壁的大面积不可再血管化疤痕上进行了 PeriCord 植入的手术。同时在非梗塞区域进行了冠状动脉旁路移植术。植入时，16cm 的心包支架含有 12.5×10 个活 WJ-MSCs（细胞活力 85.4%；<0.51 内毒素单位（EU）/mL）。术中 PeriCord 输送迅速，并使用手术胶固定。术后过程中，患者对 PeriCord 无不良反应，无需宿主免疫抑制。三个月的临床随访无异常，三个月的心脏磁共振成像显示治疗区域的疤痕质量减少了约 9%。
解释
本初步报告描述了一种可扩展的临床大小同种异体 PeriCord 心脏生物植入物的开发及其首次人体植入。
资金
La Marató de TV3 基金会、加泰罗尼亚政府、加泰罗尼亚心脏病学会、“La Caixa”银行基金会、西班牙科学、创新和大学部、西班牙卡洛斯三世健康研究所和欧洲区域发展基金。
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