Regenerative Medicine, Disease Modelling, and Drug Discovery in Human Pluripotent Stem Cell-Derived Kidney Tissue

Navin Gupta,1-3 Koichiro Susa,1,2 *Ryuji Morizane1-3

1. Renal Division, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
2. Harvard Medical School, Boston, Massachusetts, USA
3. Harvard Stem Cell Institute, Cambridge, Massachusetts, USA
*Correspondence to morizanr@da2.so-net.ne.jp

Disclosure: Ryuji Morizane is a co-inventor on patents (PCT/US16/52350) on organoid technologies that are assigned to Partners Healthcare. Navin Gupta and Koichiro Susa declare no conflicts of interest.
Acknowledgements: Research reported in this publication was supported by a National Institutes of Health (NIH) T32 fellowship training grant to Navin Gupta; a Harvard Stem Cell Institute (HSCI) Cross-Disciplinary Fellowship Grant to Navin Gupta; a Brigham and Women’s Hospital Research Excellence Award to Navin Gupta and Ryuji Morizane; the Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers, from the Japan Society for the Promotion of Science, to Koichiro Susa; the Uehara Memorial Foundation Research Fellowship for Research Abroad to Ryuji Morizane; a Grant-in-Aid for a Japanese Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad to Ryuji Morizane; a ReproCELL Stem Cell Research grant to Ryuji Morizane; a Brigham and Women’s Hospital Faculty Career Development Award to Ryuji Morizane; a Harvard Stem Cell Institute Seed Grant to Ryuji Morizane; a AJINOMOTO Co., Inc. grant to Ryuji Morizane, and a Toray Industries, Inc. grant to Ryuji Morizane.
Received: 27.03.17 Accepted: 25.07.17
Citation: EMJ Repro Health. 2017;3[1]:57-67.

Abstract

The multitude of research clarifying critical factors in embryonic organ development has been instrumental in human stem cell research. Mammalian organogenesis serves as the archetype for directed differentiation protocols, subdividing the process into a series of distinct intermediate stages that can be chemically induced and monitored for the expression of stage-specific markers. Significant advances over the past few years include established directed differentiation protocols of human embryonic stem cells and human induced pluripotent stem cells (hiPSC) into human kidney organoids in vitro. Human kidney tissue in vitro simulates the in vivo response when subjected to nephrotoxins, providing a novel screening platform during drug discovery to facilitate identification of lead candidates, reduce developmental expenditures, and reduce future rates of drug-induced acute kidney injury. Patient-derived hiPSC, which bear naturally occurring DNA mutations, may allow for modelling of human genetic diseases to enable determination of pathological mechanisms and screening for novel therapeutics. In addition, recent advances in genome editing with clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 enable the generation of specific mutations to study genetic disease, with non-mutated lines serving as an ideal isogenic control. The growing population of patients with end-stage kidney disease is a worldwide healthcare problem, with high morbidity and mortality rates, that warrants the discovery of novel forms of renal replacement therapy. Coupling the outlined advances in hiPSC research with innovative bioengineering techniques, such as decellularised kidney and three-dimensional printed scaffolds, may contribute to the development of bioengineered transplantable human kidney tissue as a means of renal replacement therapy.

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