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再生心脏:一种旨在对整个心脏器官进行保守去细胞化处理的省时、低浓度、基于去污剂的方法。

RegenHeart: A Time-Effective, Low-Concentration, Detergent-Based Method Aiming for Conservative Decellularization of the Whole Heart Organ.

作者信息

Dal Sasso Eleonora, Menabò Roberta, Agrillo Davide, Arrigoni Giorgio, Franchin Cinzia, Giraudo Chiara, Filippi Andrea, Borile Giulia, Ascione Guido, Zanella Fabio, Fabozzo Assunta, Motta Raffaella, Romanato Filippo, Di Lisa Fabio, Iop Laura, Gerosa Gino

机构信息

Cardiovascular Regenerative Medicine, Department of Cardiac Thoracic Vascular Sciences and Public Health, University of Padua, Padua 35128, Italy.

Institute of Neuroscience, National Research Council (CNR), Padua 35127, Italy.

出版信息

ACS Biomater Sci Eng. 2020 Oct 12;6(10):5493-5506. doi: 10.1021/acsbiomaterials.0c00540. Epub 2020 Sep 10.

Abstract

Heart failure is the worst outcome of all cardiovascular diseases and still represents nowadays the leading cause of mortality with no effective clinical treatments, apart from organ transplantation with allogeneic or artificial substitutes. Although applied as the gold standard, allogeneic heart transplantation cannot be considered a permanent clinical answer because of several drawbacks, as the side effects of administered immunosuppressive therapies. For the increasing number of heart failure patients, a biological cardiac substitute based on a decellularized organ and autologous cells might be the lifelong, biocompatible solution free from the need for immunosuppression regimen. A novel decellularization method is here proposed and tested on rat hearts in order to reduce the concentration and incubation time with cytotoxic detergents needed to render acellular these organs. By protease inhibition, antioxidation, and excitation-contraction uncoupling in simultaneous perfusion/submersion modality, a strongly limited exposure to detergents was sufficient to generate very well-preserved acellular hearts with unaltered extracellular matrix macro- and microarchitecture, as well as bioactivity.

摘要

心力衰竭是所有心血管疾病中最严重的后果,如今仍是主要的死亡原因,除了使用同种异体或人工替代品进行器官移植外,尚无有效的临床治疗方法。尽管同种异体心脏移植被用作金标准,但由于存在一些缺点,如免疫抑制疗法的副作用,它不能被视为永久性的临床解决方案。对于越来越多的心力衰竭患者来说,一种基于去细胞化器官和自体细胞的生物心脏替代品可能是无需免疫抑制方案的终身生物相容性解决方案。本文提出了一种新型去细胞化方法,并在大鼠心脏上进行了测试,以减少使这些器官脱细胞所需的细胞毒性去污剂的浓度和孵育时间。通过在同时灌注/浸没模式下进行蛋白酶抑制、抗氧化和兴奋-收缩解偶联,对去污剂的强烈有限暴露足以产生保存非常完好的脱细胞心脏,其细胞外基质的宏观和微观结构以及生物活性均未改变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5c2/8011801/5a349e3a5a04/ab0c00540_0001.jpg

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