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Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis
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Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis
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Journal Article
Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis
2015
Overview
The kidney arises from two types of progenitors; here, the signalling conditions that induce the production of collecting ducts and functional nephrons from human pluripotent stem cells are determined, and organoids that recapitulate the functional regionalization of the kidney are produced.
Human kidney organoids with all renal components
The development of the human kidney in the embryo depends on two different stem cell types, one to generate collecting ducts and the other to generate functional nephrons. Melissa Little, Minoru Takasato and colleagues showed previously that human pluripotent stem cells (hPSCs) can differentiate into both types of progenitors. They have now identified the signalling conditions required to induce not only these structures but also the surrounding cell types including interstitium and blood vessels. Using this approach, they have grown kidney organoids that recapitulate the functional regionalization of the embryonic kidney. The tissue complexity and degree of functionalization achieved in these organoids are not on a par with a working kidney, but replicate the normal human embryonic kidney. Importantly, they provide evidence of their potential in screening drugs for toxicity, modelling genetic kidney disease or perhaps to provide specific kidney cell types for cellular therapy.
The human kidney contains up to 2 million epithelial nephrons responsible for blood filtration. Regenerating the kidney requires the induction of the more than 20 distinct cell types required for excretion and the regulation of pH, and electrolyte and fluid balance. We have previously described the simultaneous induction of progenitors for both collecting duct and nephrons via the directed differentiation of human pluripotent stem cells
1
. Paradoxically, although both are of intermediate mesoderm in origin, collecting duct and nephrons have distinct temporospatial origins. Here we identify the developmental mechanism regulating the preferential induction of collecting duct versus kidney mesenchyme progenitors. Using this knowledge, we have generated kidney organoids that contain nephrons associated with a collecting duct network surrounded by renal interstitium and endothelial cells. Within these organoids, individual nephrons segment into distal and proximal tubules, early loops of Henle, and glomeruli containing podocytes elaborating foot processes and undergoing vascularization. When transcription profiles of kidney organoids were compared to human fetal tissues, they showed highest congruence with first trimester human kidney. Furthermore, the proximal tubules endocytose dextran and differentially apoptose in response to cisplatin, a nephrotoxicant. Such kidney organoids represent powerful models of the human organ for future applications, including nephrotoxicity screening, disease modelling and as a source of cells for therapy.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/100
/ 13/106
/ 14/19
/ 38/77
/ 49/91
/ 96/34
/ Analysis
/ Animals
/ Humanities and Social Sciences
/ Humans
/ Induced Pluripotent Stem Cells - cytology
/ Kidney Tubules, Collecting - cytology
/ Kidney Tubules, Proximal - cytology
/ Kidney Tubules, Proximal - embryology
/ Kidney Tubules, Proximal - physiology
/ Kidneys
/ letter
/ Mice
/ Nephrons - anatomy & histology
/ Rodents
/ Science
