Directed Differentiation of Pluripotent Stem Cells to Kidney Cells

Abstract

Summary 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.

Engineering Prostate Cancer from Induced Pluripotent Stem Cells—New Opportunities to Develop Preclinical Tools in Prostate and Prostate Cancer Studies

“…Successful reprogramming of prostate tissue and prostate-directed differentiation of iPSCs has been demonstrated, providing scope for such studies in the prostate field [69,70]. Many differentiation protocols towards 2D disease-relevant cell types have been described [71][72][73][74][75][76]. Furthermore, iPSCs are patient-specific and can mimic patients' phenotypes.…”

Percutaneous intrarenal transplantation of differentiated induced pluripotent stem cells into newborn mice

“…A cocktail of three differentiation factors were used. Activin A which is responsible for initial differentiation into endoderm (Picollet-D'hahan, Dolega, Freida, Martin, & Gidrol, 2017) and metanephric mesenchyme (Lam, Freedman, & Bonventre, 2014); and the addition of retinoic acid and bone morphogenetic protein 7 (BMP7), driving factors for the later maturation of the podocytes which are likely to be originated from intermediate mesoderm (Picollet-D'hahan et al, 2017). iPSCs were seeded at 15,000 cells/cm 2 and the differentiation factors added when cells were 50-60% confluent using DMEM/F12 + GlutaMAX™ media supplemented with 2-Mercaptoethanol (Gibco™, 21,985-023), 10 mM NEAA, penicillin (100 U/ml)/streptomycin (100 μg/ml; Gibco™) and 10% fetal bovine serum (FBS).…”

A comprehensive review on application of stem cells for kidney diseases

“…A great differentiation and proliferative capacity. Each of the three embryonic layers of germs developed from more than one mature somatic cell in the differentiation property (ectoderm, mesoderm, and endoderm) and second consisted of self-renewal, which has the ability to replicate to expand extensively without undergoing differentiation (Lam et al, 2014). Pluripotent SCs mammals, which include human during the embryonic development exhaust progressively this can affect insuf icient stem cell/progenitor cells.…”