Kidney organoids in translational medicine: Disease modeling and regenerative medicine

doi:10.1002/dvdy.22

Review

. 2020 Jan;249(1):34-45.

doi: 10.1002/dvdy.22. Epub 2019 Mar 26.

Kidney organoids in translational medicine: Disease modeling and regenerative medicine

Tomoya Miyoshi¹, Ken Hiratsuka^{1

2}, Edgar Garcia Saiz¹, Ryuji Morizane^{1

2

3

4}

Affiliations

¹ Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
² Department of Medicine, Harvard Medical School, Boston, Massachusetts.
³ Harvard Stem Cell Institute, Cambridge, Massachusetts.
⁴ Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts.

PMID: 30843293
PMCID: PMC6731163
DOI: 10.1002/dvdy.22

Free PMC article

Review

Kidney organoids in translational medicine: Disease modeling and regenerative medicine

Tomoya Miyoshi et al. Dev Dyn. 2020 Jan.

Free PMC article

. 2020 Jan;249(1):34-45.

doi: 10.1002/dvdy.22. Epub 2019 Mar 26.

Authors

Tomoya Miyoshi¹, Ken Hiratsuka^{1

2}, Edgar Garcia Saiz¹, Ryuji Morizane^{1

2

3

4}

Affiliations

¹ Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
² Department of Medicine, Harvard Medical School, Boston, Massachusetts.
³ Harvard Stem Cell Institute, Cambridge, Massachusetts.
⁴ Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts.

PMID: 30843293
PMCID: PMC6731163
DOI: 10.1002/dvdy.22

Abstract

The kidney is one of the most complex organs composed of multiple cell types, functioning to maintain homeostasis by means of the filtering of metabolic wastes, balancing of blood electrolytes, and adjustment of blood pressure. Recent advances in 3D culture technologies in vitro enabled the generation of "organoids" which mimic the structure and function of in vivo organs. Organoid technology has allowed for new insights into human organ development and human pathophysiology, with great potential for translational research. Increasing evidence shows that kidney organoids are a useful platform for disease modeling of genetic kidney diseases when derived from genetic patient iPSCs and/or CRISPR-mutated stem cells. Although single cell RNA-seq studies highlight the technical difficulties underlying kidney organoid generation reproducibility and variation in differentiation protocols, kidney organoids still hold great potential to understand kidney pathophysiology as applied to kidney injury and fibrosis. In this review, we summarize various studies of kidney organoids, disease modeling, genome-editing, and bioengineering, and additionally discuss the potential of and current challenges to kidney organoid research.

Keywords: disease modeling; kidney; nephron; organoid; pluripotent stem cell; regeneration.

PubMed Disclaimer

Figures

**Fig. 1.**
Disease modeling using genome editing and hPSC-derived kidney organoids.

**Fig. 2.**
Approaches to develop regenerative therapy for kidney patients using hPSCs and genome editing.

See this image and copyright information in PMC

Cited by

Organ Chips and Visualization of Biological Systems.
Tian T, Liu J, Zhu H. Tian T, et al. Adv Exp Med Biol. 2023;1199:155-183. doi: 10.1007/978-981-32-9902-3_8. Adv Exp Med Biol. 2023. PMID: 37460731
Sustained in vivo perfusion of a re-endothelialized tissue engineered kidney graft in a human-scale animal model.
Uzarski JS, Beck EC, Russell EE, Vanderslice EJ, Holzner ML, Wadhera V, Adamson D, Shapiro R, Davidow DS, Ross JJ, Florman SS. Uzarski JS, et al. Front Bioeng Biotechnol. 2023 Jun 14;11:1184408. doi: 10.3389/fbioe.2023.1184408. eCollection 2023. Front Bioeng Biotechnol. 2023. PMID: 37388767 Free PMC article.
Revolutionizing Disease Modeling: The Emergence of Organoids in Cellular Systems.
Silva-Pedrosa R, Salgado AJ, Ferreira PE. Silva-Pedrosa R, et al. Cells. 2023 Mar 18;12(6):930. doi: 10.3390/cells12060930. Cells. 2023. PMID: 36980271 Free PMC article. Review.
Extended longevity geometrically-inverted proximal tubule organoids.
Parigoris E, Lee JH, Liu AY, Zhao X, Takayama S. Parigoris E, et al. Biomaterials. 2022 Nov;290:121828. doi: 10.1016/j.biomaterials.2022.121828. Epub 2022 Oct 3. Biomaterials. 2022. PMID: 36215909 Free PMC article.
Live functional assays reveal longitudinal maturation of transepithelial transport in kidney organoids.
Rizki-Safitri A, Gupta N, Hiratsuka K, Kobayashi K, Zhang C, Ida K, Satlin LM, Morizane R. Rizki-Safitri A, et al. Front Cell Dev Biol. 2022 Aug 15;10:978888. doi: 10.3389/fcell.2022.978888. eCollection 2022. Front Cell Dev Biol. 2022. PMID: 36046340 Free PMC article.

See all "Cited by" articles

References

1. Ameku T, Taura D, Sone M, Numata T, Nakamura M, Shiota F, Toyoda T, Matsui S, Araoka T, Yasuno T, Mae S, Kobayashi H, Kondo N, Kitaoka F, Amano N, Arai S, Ichisaka T, Matsuura N, Inoue S, Yamamoto T, Takahashi K, Asaka I, Yamada Y, Ubara Y, Muso E, Fukatsu A, Watanabe A, Sato Y, Nakahata T, Mori Y, Koizumi A, Nakao K, Yamanaka S, Osafune K. 2016. Identification of MMP1 as a novel risk factor for intracranial aneurysms in ADPKD using iPSC models. Sci Rep 6:30013. - PMC - PubMed
1. Bantounas I, Ranjzad P, Tengku F, Silajdzic E, Forster D, Asselin MC, Lewis P, Lennon R, Plagge A, Wang Q, Woolf AS, Kimber SJ. 2018. Generation of Functioning Nephrons by Implanting Human Pluripotent Stem Cell-Derived Kidney Progenitors. Stem Cell Reports 10:766–779. - PMC - PubMed
1. Barker N, Huch M, Kujala P, van de Wetering M, Snippert HJ, van Es JH, Sato T, Stange DE, Begthel H, van den Born M, Danenberg E, van den Brink S, Korving J, Abo A, Peters PJ, Wright N, Poulsom R, Clevers H. 2010. Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell 6:25–36. - PubMed
1. Bartfeld S, Bayram T, van de Wetering M, Huch M, Begthel H, Kujala P, Vries R, Peters PJ, Clevers H. 2015. In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection. Gastroenterology 148:126–136 e126. - PMC - PubMed
1. Bartfeld S, Clevers H. 2015. Organoids as Model for Infectious Diseases: Culture of Human and Murine Stomach Organoids and Microinjection of Helicobacter Pylori. J Vis Exp. - PMC - PubMed

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Medical
- Genetic Alliance

[1] Ameku T, Taura D, Sone M, Numata T, Nakamura M, Shiota F, Toyoda T, Matsui S, Araoka T, Yasuno T, Mae S, Kobayashi H, Kondo N, Kitaoka F, Amano N, Arai S, Ichisaka T, Matsuura N, Inoue S, Yamamoto T, Takahashi K, Asaka I, Yamada Y, Ubara Y, Muso E, Fukatsu A, Watanabe A, Sato Y, Nakahata T, Mori Y, Koizumi A, Nakao K, Yamanaka S, Osafune K. 2016. Identification of MMP1 as a novel risk factor for intracranial aneurysms in ADPKD using iPSC models. Sci Rep 6:30013. - PMC - PubMed

[2] Ameku T, Taura D, Sone M, Numata T, Nakamura M, Shiota F, Toyoda T, Matsui S, Araoka T, Yasuno T, Mae S, Kobayashi H, Kondo N, Kitaoka F, Amano N, Arai S, Ichisaka T, Matsuura N, Inoue S, Yamamoto T, Takahashi K, Asaka I, Yamada Y, Ubara Y, Muso E, Fukatsu A, Watanabe A, Sato Y, Nakahata T, Mori Y, Koizumi A, Nakao K, Yamanaka S, Osafune K. 2016. Identification of MMP1 as a novel risk factor for intracranial aneurysms in ADPKD using iPSC models. Sci Rep 6:30013. - PMC - PubMed

[3] Bantounas I, Ranjzad P, Tengku F, Silajdzic E, Forster D, Asselin MC, Lewis P, Lennon R, Plagge A, Wang Q, Woolf AS, Kimber SJ. 2018. Generation of Functioning Nephrons by Implanting Human Pluripotent Stem Cell-Derived Kidney Progenitors. Stem Cell Reports 10:766–779. - PMC - PubMed

[4] Bantounas I, Ranjzad P, Tengku F, Silajdzic E, Forster D, Asselin MC, Lewis P, Lennon R, Plagge A, Wang Q, Woolf AS, Kimber SJ. 2018. Generation of Functioning Nephrons by Implanting Human Pluripotent Stem Cell-Derived Kidney Progenitors. Stem Cell Reports 10:766–779. - PMC - PubMed

[5] Barker N, Huch M, Kujala P, van de Wetering M, Snippert HJ, van Es JH, Sato T, Stange DE, Begthel H, van den Born M, Danenberg E, van den Brink S, Korving J, Abo A, Peters PJ, Wright N, Poulsom R, Clevers H. 2010. Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell 6:25–36. - PubMed

[6] Barker N, Huch M, Kujala P, van de Wetering M, Snippert HJ, van Es JH, Sato T, Stange DE, Begthel H, van den Born M, Danenberg E, van den Brink S, Korving J, Abo A, Peters PJ, Wright N, Poulsom R, Clevers H. 2010. Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell 6:25–36. - PubMed

[7] Bartfeld S, Bayram T, van de Wetering M, Huch M, Begthel H, Kujala P, Vries R, Peters PJ, Clevers H. 2015. In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection. Gastroenterology 148:126–136 e126. - PMC - PubMed

[8] Bartfeld S, Bayram T, van de Wetering M, Huch M, Begthel H, Kujala P, Vries R, Peters PJ, Clevers H. 2015. In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection. Gastroenterology 148:126–136 e126. - PMC - PubMed

[9] Bartfeld S, Clevers H. 2015. Organoids as Model for Infectious Diseases: Culture of Human and Murine Stomach Organoids and Microinjection of Helicobacter Pylori. J Vis Exp. - PMC - PubMed

[10] Bartfeld S, Clevers H. 2015. Organoids as Model for Infectious Diseases: Culture of Human and Murine Stomach Organoids and Microinjection of Helicobacter Pylori. J Vis Exp. - PMC - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Kidney organoids in translational medicine: Disease modeling and regenerative medicine

Affiliations

Kidney organoids in translational medicine: Disease modeling and regenerative medicine

Authors

Affiliations

Abstract

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Abstract

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Medical