Generation of functioning nephrons by implanting human pluripotent stem cell-derived kidney progenitors

Bantounas, Ioannis and Ranjzad, Parisa and Tengku Zakaria, Tengku Muhamad Faris Syafiq and Silajdžić, Edina and Forster, Duncan and Asselin, Marie-Claude and Lewis, Philip and Lennon, Rachel and Plagge, Antonius and Wang, Qi and Woolf, Adrian S. and Kimber, Susan J. (2018) Generation of functioning nephrons by implanting human pluripotent stem cell-derived kidney progenitors. Stem Cell Reports, 10 (3). pp. 766-779. ISSN 2213-6711

PDF (Article (Full Text)) - Published Version Restricted to Repository staff only Download (5MB) | Request a copy

Abstract

Human pluripotent stem cells (hPSCs) hold great promise for understanding kidney development and disease. We reproducibly differentiated three genetically distinct wild-type hPSC lines to kidney precursors that underwent rudimentary morphogenesis in vitro. They expressed nephron and collecting duct lineage marker genes, several of which are mutated in human kidney disease. Lentiviral-transduced hPSCs expressing reporter genes differentiated similarly to controls in vitro. Kidney progenitors were subcutaneously implanted into immunodeficient mice. By 12 weeks, they formed organ-like masses detectable by bioluminescence imaging. Implants included perfused glomeruli containing human capillaries, podocytes with regions of mature basement membrane, and mesangial cells. After intravenous injection of fluorescent low-molecular-weight dextran, signal was detected in tubules, demonstrating uptake from glomerular filtrate. Thus, we have developed methods to trace hPSC-derived kidney precursors that formed functioning nephrons in vivo. These advances beyond in vitro culture are critical steps toward using hPSCs to model and treat kidney diseases.

Item Type:	Article (Journal)
Additional Information:	9893/84383
Uncontrolled Keywords:	cell therapy; glomerulus; human embryonic stem cells; kidney; kidney progenitors; lentivirus; metanephric mesenchyme; nephron; ureteric epithelium; vascularization.
Subjects:	R Medicine > R Medicine (General)
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Nursing Kulliyyah of Nursing > Department of Basic Medical Sciences for Nursing
Depositing User:	Asst Prof Tengku Faris
Date Deposited:	03 Nov 2020 15:28
Last Modified:	03 Nov 2020 15:28
URI:	http://irep.iium.edu.my/id/eprint/84383

Actions (login required)

View Item