Kirsty M Rooney1, Adrian S Woolf1,2, Susan J Kimber1. 1. Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester, United Kingdom. 2. Royal Manchester Children's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Abstract
BACKGROUND: Kidney disease causes major suffering and premature mortality worldwide. With no cure for kidney failure currently available, and with limited options for treatment, there is an urgent need to develop effective pharmaceutical interventions to slow or prevent kidney disease progression. SUMMARY: In this review, we consider the feasibility of using human pluripotent stem cell-derived kidney tissues, or organoids, to model genetic kidney disease. Notable successes have been made in modelling genetic tubular diseases (e.g., cystinosis), polycystic kidney disease, and medullary cystic kidney disease. Organoid models have also been used to test novel therapies that ameliorate aberrant cell biology. Some progress has been made in modelling congenital glomerular disease, even though glomeruli within organoids are developmentally immature. Less progress has been made in modelling structural kidney malformations, perhaps because sufficiently mature metanephric mesenchyme-derived nephrons, ureteric bud-derived branching collecting ducts, and a prominent stromal cell population are not generated together within a single protocol. Key Messages: We predict that the field will advance significantly if organoids can be generated with a full complement of cell lineages and with kidney components displaying key physiological functions, such as glomerular filtration. The future economic upscaling of reproducible organoid generation will facilitate more widespread research applications, including the potential therapeutic application of these stem cell-based technologies.
BACKGROUND: Kidney disease causes major suffering and premature mortality worldwide. With no cure for kidney failure currently available, and with limited options for treatment, there is an urgent need to develop effective pharmaceutical interventions to slow or prevent kidney disease progression. SUMMARY: In this review, we consider the feasibility of using human pluripotent stem cell-derived kidney tissues, or organoids, to model genetic kidney disease. Notable successes have been made in modelling genetic tubular diseases (e.g., cystinosis), polycystic kidney disease, and medullary cystic kidney disease. Organoid models have also been used to test novel therapies that ameliorate aberrant cell biology. Some progress has been made in modelling congenital glomerular disease, even though glomeruli within organoids are developmentally immature. Less progress has been made in modelling structural kidney malformations, perhaps because sufficiently mature metanephric mesenchyme-derived nephrons, ureteric bud-derived branching collecting ducts, and a prominent stromal cell population are not generated together within a single protocol. Key Messages: We predict that the field will advance significantly if organoids can be generated with a full complement of cell lineages and with kidney components displaying key physiological functions, such as glomerular filtration. The future economic upscaling of reproducible organoid generation will facilitate more widespread research applications, including the potential therapeutic application of these stem cell-based technologies.
Authors: Sarah Williams; Joseph L Charest; Martin R Pollak; Balajikarthick Subramanian Journal: Tissue Eng Part B Rev Date: 2021-12-08 Impact factor: 7.376
Authors: Mychel R P T Morais; Pinyuan Tian; Craig Lawless; Syed Murtuza-Baker; Louise Hopkinson; Steven Woods; Aleksandr Mironov; David A Long; Daniel P Gale; Telma M T Zorn; Susan J Kimber; Roy Zent; Rachel Lennon Journal: Elife Date: 2022-01-25 Impact factor: 8.713