Kidney organoids as a promising tool in nephrology

Abstract

Kidney disease has become a global public health problem affecting over 750 million people worldwide and imposing a heavy economic burden on patients. The complex architecture of the human kidney makes it very difficult to study the pathophysiology of renal diseases in vitro and to develop effective therapeutic options for patients. Even though cell lines and animal models have enriched our understanding, they fail to recapitulate key aspects of human kidney development and renal disease at cellular and functional levels. Organoids can be derived from either pluripotent stem cells or adult stem cells by strictly regulating key signalling pathways. Today, these self-differentiated organoids represent a promising technology to further understand the human kidney, one of the most complex organs, in an unprecedented way. The newly established protocols improved by organ-on-chip and coculture with immune cells will push kidney organoids towards the next generation. Herein, we focus on recent achievements in the application of kidney organoids in disease modelling, nephrotoxic testing, precision medicine, biobanking, and regenerative therapy, followed by discussions of novel strategies to improve their utility for biomedical research. The applications we discuss may help to provide new ideas in clinical fields.

Keywords: Biomedical research; Disease modelling; Kidney organoids; Precision medicine; Stem cells.

Figure 1

Density map of main keywords. Note: The brightness of the color is positively correlated with the frequency of keywords.

Figure 2

Network map of studies on kidney organoids around the world. (A) Network map of 26 authors with frequency greater than five. (B) Countries involved studies on kidney organoids. (C) Network map of 49 institutions with frequency greater than five. Note: The nodes represent the number of frequency, the links between nodes represent collaboration, and different colors of nodes represent different clusters.

Figure 3

Characteristics of the three mainstream preclinical kidney diseases models.

Figure 4

Potential applications in disease modelling, nephrotoxic testing, precision medicine, biobanking and regenerative therapy. (A) Organoids from patient-derived tissues or iPSCs/ASCs can be used to model diseases through genetic manipulations. (B) Nephrotoxicity testing can be constructed on a large scale. (C) Organoids facilitate the development of personalized medicine and drug discovery. (D) Organoids serve as a renewable resource in biobanking. (E) The ultimate goal of organoids is to generate functional human organs for regenerative medicine.