肾脏类器官的构建及其应用

Construction of kidney organoid and its application

  • 摘要: 肾移植是终末期肾病的重要治疗方式,但其长期疗效仍受供肾短缺、供肾质量下降、缺血-再灌注损伤、排斥反应和慢性移植物失功等因素限制。传统监测手段在灵敏度、特异度和动态评估方面存在不足,亟需建立更接近人肾脏发育、结构和功能特征的新型研究模型。肾脏类器官是由干细胞或祖细胞在三维培养条件下形成的器官样结构,广义上包括诱导多能干细胞(iPSC)来源肾脏类器官以及成体或原代来源肾小管类器官。本文重点围绕iPSC来源肾脏类器官展开,系统概述其定义、发展历程及在肾脏发育机制研究、遗传性和获得性肾病建模、药物筛选与肾毒性评价、精准医学研究中的应用。近年来,随着诱导分化体系、祖细胞扩增、血管化工程、收集系统整合和空间组装策略的不断发展,肾脏类器官在器官移植领域显示出重要潜力,可用于移植免疫机制研究、排斥反应模拟、移植后疾病复发风险评估、供肾离体修复和常温机械灌注递送等转化前研究。现阶段,肾脏类器官尚不能替代整肾移植,其临床转化仍受成熟度不足、血管整合有限、尿液引流通路不完善、异位分化及长期安全性不确定等因素制约。未来,构建同时具备稳定血管化、持续滤过、有效引流和宿主长期功能整合能力的工程化肾组织,将是推动肾脏类器官从基础研究迈向移植转化应用的关键方向。

     

    Abstract: Kidney transplantation is an important treatment method for end-stage renal disease, but its long-term efficacy is still limited by factors such as shortage of donor kidneys, decline in donor kidney quality, ischemia-reperfusion injury, rejection reactions and chronic graft failure. Traditional monitoring methods have deficiencies in sensitivity, specificity and dynamic assessment, and there is an urgent need to establish new research models that are closer to the development, structure and functional characteristics of human kidneys. Kidney organoids are organ-like structures formed by stem cells or progenitor cells under three-dimensional culture conditions. Broadly speaking, they include kidney organoids derived from induced pluripotent stem cell (iPSC) and renal tubule organoids from adult or primary sources. This article focuses on iPSC-derived kidney organoids and systematically summarizes their definition, development history and applications in the study of kidney development mechanisms, modeling of hereditary and acquired kidney diseases, drug screening and evaluation of renal toxicity, and precision medicine research. In recent years, with the continuous development of induction differentiation systems, progenitor cell expansion, vascularization engineering, collection system integration and spatial assembly strategies, kidney organoids have shown significant potential in the field of organ transplantation and can be used for pre-translation research such as study of transplantation immune mechanisms, simulation of rejection, assessment of recurrence risk after transplantation, in vitro repair of donor kidneys and normothermic mechanical perfusion delivery. Currently, kidney organoids cannot replace whole kidney transplantation, and their clinical translation is still constrained by factors such as insufficient maturity, limited vascular integration, incomplete urine drainage pathways, ectopic differentiation and uncertainty of long-term safety. In the future, constructing engineered kidney tissues with stable vascularization, continuous filtration, effective drainage and long-term host functional integration capabilities will be a key direction for promoting kidney organoids from basic research to transplantation transformation applications.

     

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