195accelerated by acute or chronic kidney diseases, and while tubular epithelial cells
can respond to elicit repair following mild-moderate acute tubular injury (Smeets
et al. 2013 ; Berger et al. 2014 ), there is no persisting postnatal nephron progenitor
cell population to regenerate new filtration units (Hartman et al. 2007 ; Rumballe
et al. 2011 ). End-stage kidney disease occurs when approximately 90% of func-
tional filtration is lost and results in considerable morbidity, mortality and health-
care expenditure. Despite advances in dialysis and kidney transplantation, these
renal replacement therapies remain expensive and resource-limited interventions
with significant complications.
The concept of regeneration of renal tissue is appealing in both research and
clinical nephrology; however, the structural and functional complexity of the kidney
makes it arguably one of the most complex tissues to regenerate in vitro. Many
protocols have been published towards this aim (Wang et al. 2013 ; Takasato et al.
2014 ; Taguchi et al. 2014 ; Lam et al. 2014a; Freedman et al. 2015 ; Morizane et al.
2015 ), including a recent protocol that successfully derived kidney organoids from
iPSCs containing ureteric epithelial collecting ducts, nephron, stromal and vascular
progenitors as well as early nephrons which segment into proximal and distal
tubules and immature glomeruli (Takasato et al. 2015 ). In this chapter, we discuss
the current understanding of mammalian kidney development and the application of
this knowledge to the formulation of protocols for the differentiation of human plu-
ripotent stem cells (hPSCs) to multicellular kidney organoids. We discuss the poten-
tial applications and limitations of kidney organoids in the research of human kidney
development, drug nephrotoxicity screening and kidney injury, repair and disease
modelling. Finally, we discuss progress towards clinical regenerative therapies aris-
ing from these advances.
Fig. 11.1 Structure of the kidney. A single nephron illustrating the complex anatomy and archi-
tecture of the different segments and cell types and a description of their varied, specialised func-
tions. GBM, glomerular basement membrane; AQP2, aquaporin 2; AVP, arginine vasopressin;
EPO, erythropoietin
11 Recapitulating Development to Generate Kidney Organoid Cultures