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中华肾病研究电子杂志 ›› 2022, Vol. 11 ›› Issue (04) : 224 -230. doi: 10.3877/cma.j.issn.2095-3216.2022.04.008

综述

人工肾的研究进展
于茜1, 周建辉1,(), 谢大洋1, 杨巧巧1, 赵小淋1, 王宏1   
  1. 1. 100853 北京,解放军总医院第一医学中心肾脏病科、解放军肾脏病研究所、肾脏疾病国家重点实验室、国家慢性肾病临床医学研究中心、肾脏疾病研究北京市重点实验室
  • 收稿日期:2022-01-06 出版日期:2022-08-28
  • 通信作者: 周建辉
  • 基金资助:
    先进医疗装备示范应用项目(2018MND102031)

Progress in the research on artificial kidney

Qian Yu1, Jianhui Zhou1,(), Dayang Xie1, Qiaoqiao Yang1, Xiaolin Zhao1, Hong Wang1   

  1. 1. Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Beijing 100853, China
  • Received:2022-01-06 Published:2022-08-28
  • Corresponding author: Jianhui Zhou
引用本文:

于茜, 周建辉, 谢大洋, 杨巧巧, 赵小淋, 王宏. 人工肾的研究进展[J]. 中华肾病研究电子杂志, 2022, 11(04): 224-230.

Qian Yu, Jianhui Zhou, Dayang Xie, Qiaoqiao Yang, Xiaolin Zhao, Hong Wang. Progress in the research on artificial kidney[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2022, 11(04): 224-230.

人工肾发展源于肾脏替代治疗的研究,期待能造福尿毒症群体。其方向逐渐突破血液净化常规思维,迈向更全面、更多样的血液净化理念。本文介绍了多种便携式血液净化单元原理及多项研究成果,并详细介绍了细胞工程技术、芯片技术、3D打印技术及异种移植方面的人工肾研究最新进展。

The development of artificial kidney is derived from the study of renal replacement therapy, which is expected to benefit uremia patients. The direction of artificial kidney research gradually breaks through the conventional thinking of blood purification, and moves toward a more comprehensive and diversified blood purification concept. This article introduced the principle of various portable blood purification units and a number of research achievements, and expounded the latest progress in artificial kidney study, including cell engineering technology, chip technology, 3D printing technology as well as xenotransplantation.

图1 自动可穿戴腹透式人工肾工作原理示意图[15]注:ultrafiltration bag:超滤袋;storage module:存储模块;sorbent cartridge:吸附剂盒;enrichment module:补充模块;cycler controller:循环控制器;pumps:泵;battery:电池;peritoneal dialysis catheter:腹透导管;disposable module:可丢弃组件;durable module:循环组件。AWAK系统:将500ml的待用透析液从腹膜腔排到存储模块,经过吸附剂盒中清洗再生、补充电解质后返回腹膜腔,进行潮交换,多余的流体被排出在超滤袋中
图2 生物人工肾上皮细胞系统组件及构成示例[19]注:outlet:出口;inlet:入口;sample ports:样本端;disks:碳盘;baffle:挡板;flow separator:流量分离器;A:细胞在涂有铌的碳盘上生长;B:显示DAPI染色后的细胞;C:ZO-1染色(绿色)、乙酰化微管蛋白染色(红色);细胞在涂有铌的碳盘上生长,这些碳盘固定在生物人工肾上皮细胞系统内,挡板用于隔离碳盘,流量分离器位于入口处,以保持整个BRECS稳定和均匀流动
图3 多层微流体装置的制作示意图[24]注:PDMS channel:聚二甲基硅氧烷通道;porous membrane:多孔渗透膜;PDMS well:聚二甲基硅氧烷凹槽;bonding:粘合;multi-layer microfluidic device:多层微流体装置;culture dish:培养皿;inside tubular fluid:内管液体;outside tubular fluid:外管液体;renal tubule cells:肾小管细胞;top view:顶视图;cells in MMD:多层微流体装置中的细胞;A:MMD是(PDMS)通道,聚酯膜和PDMS储层通过等离子体处理粘合的夹层组件;B:MMD的操作,连接到带有硅胶管的注射泵、MMD被放置在含有外部管状流体的培养皿上;C:培养皿上装置示意图;D:MMD内IMCD细胞的显微镜图,细胞接种3 d后融合生长,该图显示通道内细胞完全隔离、无渗漏
图4 3D肾近曲小管芯片模型制作示意图[28]注:Convoluted Proximal Tubule:近曲小管;print:打印;silicone gasket:硅胶垫圈;cast:铸型;pluronic:一种非离子表面活性剂;gelatin fibrinogen:明胶纤维蛋白原;evacuate:抽空;PTECs:近曲小管上皮细胞;add cells:添加细胞;perfuse:灌注;Actin:肌动蛋白;Nuclei:细胞核;open lumen:开放的官腔;3D open lumen embeded in ECM嵌于细胞基质的3D开放腔;tubulin:微管蛋白;controlled perfusion on chip:在芯片上受控灌注;A:突出近曲小管的肾单元示意图;B和C:制作3D弯曲、可灌注近端小管的不同步骤的相应示意图和图像,在此过程中,先在明胶纤维蛋白原ECM上打印易消散油墨(i),在打印部分(ii)周围浇铸额外的ECM,将易消散的油墨抽空以创建一个开放的管形(iii),并在管内播撒PTECs细胞并长时间灌注(iv);D:通过共聚焦显微镜获得3D打印近曲小管的描绘,其中肌动蛋白染为红色,细胞核为蓝色;图中白色虚线为PTECs细胞三维包围开放腔的横切面位置,比例尺= 500 μm;E:在D图中白色矩形区域的高倍放大图,比例尺= 200 μm;F:3D肾近曲小管描绘图,在芯片上定向灌注被上皮细胞包围的开放管腔,Na+/K+-ATP酶染为红色,乙酰化微管蛋白为橙色以突出纤毛,核为蓝色,比例尺= 50 μm
图5 新型肾小管阵列系统示意图[30]注:top view:顶面观;side view:侧面观;PDMS mounting:聚二甲基硅氧烷底座;casting patterns:铸型;patterns in gels:凝胶模型;add cells:添加细胞,closure with ECM:细胞基质封闭;stamp:图印。建立肾小管阵列系统(gKT)。A:gKT建立的逐步示意图;B:系统中使用的具有代表性的PDMS印章图像;C:在ECM(胶原基质)中复制成型后的图案;D:细胞接种和ECM封闭后。比例尺:50 μm
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