Abstract
In the past five years, pluripotent stem cell (PSC)-derived kidney organoids and adult stem or progenitor cell (ASC)-based kidney tubuloids have emerged as advanced in vitro models of kidney development, physiology, and disease. PSC-derived organoids mimic nephrogenesis. After differentiation towards the kidney precursor tissues ureteric bud and metanephric mesenchyme, their reciprocal interaction causes self-organization and patterning in vitro to generate nephron structures that resemble the fetal kidney. ASC tubuloids on the other hand recapitulate renewal and repair in the adult kidney tubule and give rise to long-term expandable and genetically stable cultures that consist of adult proximal tubule, loop of Henle, distal tubule, and collecting duct epithelium. Both organoid types hold great potential for: (1) studies of kidney physiology, (2) disease modeling, (3) high-throughput screening for drug efficacy and toxicity, and (4) regenerative medicine. Currently, organoids and tubuloids are successfully used to model hereditary, infectious, toxic, metabolic, and malignant kidney diseases and to screen for effective therapies. Furthermore, a tumor tubuloid biobank was established, which allows studies of pathogenic mutations and novel drug targets in a large group of patients. In this review, we discuss the nature of kidney organoids and tubuloids and their current and future applications in science and medicine.
Highlights
Kidney disease affects around 15% of the population and is accompanied by a substantial increase in morbidity and mortality [1]
Organoids are three-dimensional (3D) multicellular cultures that resemble the structure, physiology and diseases of their organ of origin. These cultures are generated from either pluripotent stem cells (PSC) or adult stem or progenitor cells (ASC), two complementary techniques with their own characteristics and specific fields of application
In the past five years, the processes of nephrogenesis and homeostasis and regeneration in the adult kidney have been recapitulated in the laboratory to generate PSC and ASC-derived kidney organoids [4,5,6,7,8,9]
Summary
Kidney disease affects around 15% of the population and is accompanied by a substantial increase in morbidity and mortality [1]. Organoids are three-dimensional (3D) multicellular cultures that resemble the structure, physiology and diseases of their organ of origin These cultures are generated from either pluripotent stem cells (PSC) or adult stem or progenitor cells (ASC), two complementary techniques with their own characteristics and specific fields of application. In the past five years, the processes of nephrogenesis and homeostasis and regeneration in the adult kidney have been recapitulated in the laboratory to generate PSC and ASC-derived kidney organoids [4,5,6,7,8,9] These organoids hold great potential to improve our understanding of kidney disease and facilitate the discovery of new therapeutic options. We will focus on the nature of PSC and ASC-derived kidney organoids and their current and future applications in science and medicine
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