The myriad possibility of kidney organoids.

Pinyuan Tian,Rachel Lennon

doi:10.1097/mnh.0000000000000498

Pinyuan Tian, Rachel Lennon

Open Access

https://doi.org/10.1097/mnh.0000000000000498

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Abstract

Purpose of reviewHuman kidney development and the mechanisms of many kidney diseases are incompletely understood partly due to the lack of appropriate models. Kidney organoids derived from human pluripotent stem cells (hPSCs) are a new and rapidly developing in-vitro system covering the window of early nephrogenesis and having the capacity for disease modelling. The application of global analytic tools such as RNA sequencing and proteomics is providing new and unexpected insights into kidney organoids with relevance for development and disease. In this review, we focus on the most significant advances in the field over the last 2 years.Recent findingsThere have been several protocol modifications for the differentiation of hPSCs into kidney organoids, including the additional step of implantation into mice. These changes have improved the vascularization and maturity of the major cell types in the organoids, increased the production scale, and reduced the cost and labour intensity of culturing organoids. Single-cell RNA sequencing and global proteomics of kidney organoids have provided important insights into the multiple cell populations, origin of cells, and regulatory relationships between genes. There has been an increase in research using patient-derived induced pluripotent stem cells (iPSCs), or combining gene editing with iPSC-derived kidney organoids as a novel disease-modelling platform for improving our understanding of disease mechanisms, drug testing and discovery, and the potential for personalized therapy. Finally, there has been progress in culturing hPSCs-derived kidney cells in microfluidic kidney-on-a-chip devices and this may provide a means of further improving the maturity of kidney organoids.SummaryThe review summarizes the latest progress on kidney organoids including differentiation protocols, analysis tools, and applications. Despite some limitations, hPSC-derived kidney organoids are authentic and practical models for investigating kidney development and disease and progressing understanding about tissue regeneration, drug screening, and disease modelling.

Highlights

The creation of kidney structures from human pluripotent stem cells has been extensively studied in the past 5 years
The generation of induced pluripotent stem cells (iPSCs) lines requires expertise and the methods are time consuming iPSC. Resources such as the human iPSCs initiative based at the Sanger Institute in Cambridge [3] provide important platforms for researchers to study human iPSC lines generated from patients with a range of aWellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester and bDepartment of Paediatric Nephrology, Manchester University Hospitals NHS Foundation Trust, Manchester, UK
Recent updates in protocols for generating kidney organoids from human pluripotent stem cells (hPSCs) including implantation into mice; the use of automated pipelines, and spinner flasks to increase scale of cultures

Summary

INTRODUCTION

The creation of kidney structures from human pluripotent stem cells (hPSCs) has been extensively studied in the past 5 years. The generation of iPSC lines requires expertise and the methods are time consuming iPSC resources such as the human iPSCs initiative based at the Sanger Institute in Cambridge [3] provide important platforms for researchers to study human iPSC lines generated from patients with a range of aWellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester and bDepartment of Paediatric Nephrology, Manchester University Hospitals NHS Foundation Trust, Manchester, UK.

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