Models of kidney glomerulus derived from human-induced pluripotent stem cells
Human pluripotent stem cells hold tremendous promise for understanding tissue development and disease mechanisms, and for in vitro modeling of organ function. However, the use of stem cells to model and understand human kidney development had remained elusive until recent advances in the establishment of protocols for the derivation of functional human kidney cells such as glomerular podocytes and organoids, and reconstitution of glomerular tissue structure and function as well as disease models using microfluidic organ-on-a-chip microphysiological system. In this chapter, we discuss recent approaches and progress in modeling the complex architecture of the kidney glomerulus using induced pluripotent stem cells interfaced with bioengineering technologies. We also provide an overview of the anatomy and physiology of the human kidney glomerulus as well as some pathological conditions associated with this functional subunit of the kidney. An overview of kidney development is also provided along with discussions of crucial nephrogenic events, the spatiotemporal regulation of nephrogenesis through secreted factors, and how this knowledge has been applied to develop new methodologies for the derivation of kidney tissues and functional in vitro models. Together, the technologies presented in this chapter could advance the field of nephrology by providing platforms for disease modeling, nephrotoxicity testing, and drug screening.