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人工肾胶囊包被间充质干细胞水凝胶用于治疗横纹肌溶解症诱导的急性肾损伤。

Artificial Kidney Capsule Packed with Mesenchymal Stem Cell-Laden Hydrogel for the Treatment of Rhabdomyolysis-Induced Acute Kidney Injury.

机构信息

Medical School of Chinese PLA, Beijing 100853, China.

Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China.

出版信息

ACS Biomater Sci Eng. 2022 Apr 11;8(4):1726-1734. doi: 10.1021/acsbiomaterials.1c01595. Epub 2022 Mar 18.

Abstract

Acute kidney injury (AKI) has emerged as a major public health problem affecting millions of people worldwide without specific and satisfactory therapies due to the lack of an effective delivery approach. In the past few decades, hydrogels present infinite potential in localized drug delivery, while their poor adhesion to moist tissue and isotropic diffusion character always restrict the therapeutic efficiency and may lead to unwanted side effects. Herein, we proposed a novel therapeutic strategy for AKI via a customizable artificial kidney capsule (AKC) together with a mesenchymal stem cell (MSC)-laden hydrogel. Specifically, an elastic capsule owning an inner chamber with the same size and shape as the kidney is designed and fabricated through three-dimensional (3D) modeling and printing, serving as an outer wrap for kidney and cell-laden hydrogels. According to the in vitro experiment, the excellent biocompatibility of gelatin-based hydrogel ensures viability and proliferation of MSCs. In vivo mice experiments proved that this concept of AKC-assisted kidney drug delivery could efficiently reduce epithelial cell apoptosis and minimize the damage of the renal tubular structure for mice suffering AKI. Such a strategy not only provides a promising alternative in the treatment of AKI but also offers a feasible and versatile approach for the repair and recovery of other organs.

摘要

急性肾损伤(AKI)已成为一个全球性的重大公共卫生问题,影响了全球数百万人,由于缺乏有效的治疗方法,目前还没有特定且令人满意的治疗方法。在过去的几十年中,水凝胶在局部药物输送方面具有巨大的潜力,但其与湿润组织的附着力差和各向同性扩散特性始终限制了治疗效率,并可能导致不必要的副作用。在这里,我们通过定制的人工肾胶囊(AKC)和间充质干细胞(MSC)负载的水凝胶提出了一种治疗 AKI 的新策略。具体而言,通过三维(3D)建模和打印设计并制造了一个具有与肾脏相同大小和形状的内腔的弹性胶囊,用作肾脏和细胞负载水凝胶的外罩。根据体外实验,基于明胶的水凝胶具有优异的生物相容性,确保了 MSC 的活力和增殖。体内小鼠实验证明,AKC 辅助肾脏药物输送的概念可以有效减少上皮细胞凋亡,并最大程度地减少 AKI 小鼠肾脏管状结构的损伤。这种策略不仅为 AKI 的治疗提供了有前途的替代方法,而且还为其他器官的修复和恢复提供了可行且通用的方法。

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