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Directed differentiation of pluripotent stem cells to kidney cells.

Research paper by Albert Q AQ Lam, Benjamin S BS Freedman, Joseph V JV Bonventre

Indexed on: 14 Sep '14Published on: 14 Sep '14Published in: Seminars in Nephrology



Abstract

Regenerative medicine affords a promising therapeutic strategy for the treatment of patients with chronic kidney disease. Nephron progenitor cell populations exist only during embryonic kidney development. Understanding the mechanisms by which these populations arise and differentiate is integral to the challenge of generating new nephrons for therapeutic purposes. Pluripotent stem cells (PSCs), comprising embryonic stem cells, and induced pluripotent stem cells (iPSCs) derived from adults, have the potential to generate functional kidney cells and tissue. Studies in mouse and human PSCs have identified specific approaches to the addition of growth factors, including Wnt and fibroblast growth factor, that can induce PSC differentiation into cells with phenotypic characteristics of nephron progenitor populations with the capacity to form kidney-like structures. Although significant progress has been made, further studies are necessary to confirm the production of functional kidney cells and to promote their three-dimensional organization into bona fide kidney tissue. Human PSCs have been generated from patients with kidney diseases, including polycystic kidney disease, Alport syndrome, and Wilms tumor, and may be used to better understand phenotypic consequences of naturally occurring genetic mutations and to conduct "clinical trials in a dish". The capability to generate human kidney cells from PSCs has significant translational applications, including the bioengineering of functional kidney tissue, use in drug development to test compounds for efficacy and toxicity, and in vitro disease modeling.