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A novel cytoprotective organ perfusion platform for reconstructing homeostasis of DCD liver while alleviating IRI injury
Bioengineering & Translational Medicine ( IF 6.1 ) Pub Date : 2024-09-23 , DOI: 10.1002/btm2.10724
Tingting Lan, Mingxing Yu, Tao Ming, Hong Wang, Juan Deng, Shuhan Cheng, Zhongyang Shen, Deling Kong

Pump is a vital component for expelling the perfusate in small animal isolated organ normothermic machine perfusion (NMP) systems whose flexible structure and rhythmic contraction play a crucial role in maintaining perfusion system homeostasis. However, the continuous extrusion forming with the rigid stationary shaft of the peristaltic pumps can damage cells, leading to metabolic disorders and eventual dysfunction of transplanted organs. Here, we developed a novel biomimetic blood‐gas system (BBGs) for preventing cell damage. This system mimics the cardiac cycle and features an adjustable inspiratory‐to‐expiratory (IE) ratio to mitigate acidosis caused by continuous oxygen inhalation. In our study, adipose stem cells (ADSCs) were cultured within the circulatory system for 10 min, 2, and 4 h. Compared to the peristaltic pump, the BBGs significantly reduced cell apoptosis and morphological injury while enhancing cell proliferation and adhesion. Additionally, when the supernatant from ADSCs was introduced to LPS‐induced macrophages for 24 h, the BBGs group demonstrated a more pronounced anti‐inflammatory effect, characterized by reduced M1 macrophage expression. Besides, with isolated rat livers from donation after circulatory death (DCD) perfusion with ADSCs for 6 h by the BBGs, we detected fewer apoptotic cells and a reduced inflammatory response, evidenced by down‐regulated TNF‐α expression. The development of BBGs demonstrates the feasibility of recreating physiological liquid–gas circulation in vitro, offering an alternative platform for isolated organ perfusion, especially for applications involving cell therapy.

中文翻译:


一种新型细胞保护器官灌注平台,用于重建 DCD 肝脏稳态,同时减轻 IRI 损伤



泵是小动物离体器官常温机灌注(NMP)系统中排出灌注液的重要部件,其灵活的结构和节律性收缩对于维持灌注系统的稳态起着至关重要的作用。然而,蠕动泵刚性固定轴的连续挤压成型会损伤细胞,导致代谢紊乱,最终导致移植器官功能障碍。在这里,我们开发了一种新型仿生血气系统(BBG)来防止细胞损伤。该系统模仿心动周期,具有可调节的吸气与呼气 (IE) 比率,以减轻持续吸氧引起的酸中毒。在我们的研究中,脂肪干细胞 (ADSC) 在循环系统内培养 10 分钟、2 和 4 小时。与蠕动泵相比,BBG 显着减少细胞凋亡和形态损伤,同时增强细胞增殖和粘附。此外,当将 ADSC 的上清液引入 LPS 诱导的巨噬细胞 24 小时时,BBG 组表现出更明显的抗炎作用,其特点是 M1 巨噬细胞表达减少。此外,对于来自循环死亡(DCD)捐献的离体大鼠肝脏,通过 BBG 灌注 ADSC 6 小时,我们检测到凋亡细胞减少,炎症反应减少,TNF-α 表达下调证明了这一点。 BBG 的开发证明了在体外重建生理液-气循环的可行性,为离体器官灌注提供了替代平台,特别是对于涉及细胞治疗的应用。
更新日期:2024-09-23
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