Tubuloid culture enables long-term expansion of functional human kidney tubule epithelium from iPSC-derived organoids

Fjodor A. Yousef Yengej; Jitske Jansen; Carola M. E. Ammerlaan; Emre Dilmen; Carla Pou Casellas; Rosalinde Masereeuw; Joost G. Hoenderop; Bart Smeets; Maarten B. Rookmaaker; Marianne C. Verhaar; Hans Clevers

doi:10.1073/pnas.2216836120

Tubuloid culture enables long-term expansion of functional human kidney tubule epithelium from iPSC-derived organoids

Fjodor A. Yousef Yengej
, Jitske Jansen
, Carola M. E. Ammerlaan
, Emre Dilmen
, Carla Pou Casellas
, Rosalinde Masereeuw
, Joost G. Hoenderop
, Bart Smeets
, Maarten B. Rookmaaker
, Marianne C. Verhaar
, Hans Clevers

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Kidney organoids generated from induced pluripotent stem cells (iPSC) have proven valuable for studies of kidney development, disease, and therapeutic screening. However, specific applications have been hampered by limited expansion capacity, immaturity, off-target cells, and inability to access the apical side. Here, we apply recently developed tubuloid protocols to purify and propagate kidney epithelium from d7+18 (post nephrogenesis) iPSC-derived organoids. The resulting ‘iPSC organoid-derived (iPSCod)’ tubuloids can be exponentially expanded for at least 2.5 mo, while retaining expression of important tubular transporters and segment-specific markers. This approach allows for selective propagation of the mature tubular epithelium, as immature cells, stroma, and undesirable off-target cells rapidly disappeared. iPSCod tubuloids provide easy apical access, which enabled functional evaluation and demonstration of essential secretion and electrolyte reabsorption processes. In conclusion, iPSCod tubuloids provide a different, complementary human kidney model that unlocks opportunities for functional characterization, disease modeling, and regenerative nephrology.

Original language	English
Article number	e2216836120
Pages (from-to)	1-11
Number of pages	11
Journal	Proceedings of the National Academy of Sciences
Volume	120
Issue number	6
DOIs	https://doi.org/10.1073/pnas.2216836120
Publication status	Published - 7 Feb 2023

Bibliographical note

Publisher Copyright:
Copyright © 2023 the Author(s). Published by PNAS.

Funding

ACKNOWLEDGMENTS. F.A.Y.Y., C.M.E.A., C.P.C., R.M., M.B.R., and M.C.V. acknowledge the support of the partners of “Regenerative Medicine Crossing Borders” (RegMed XB), Powered by Health~Holland, Top Sector Life Sciences & Health and the Gravitation Program “Materials Driven Regeneration”, funded by the Netherlands Organization for Scientific Research (024.003.013).J.J.is supported by the Netherlands Organisation for Scientific Research (NWO Veni grant no: 091 501 61 81 01 36) and the Dutch Kidney Foundation (grant no. 19OK005). We are grateful to H. Begthel (Hubrecht Institute, the Netherlands) for preparation of some of the immunohistochemistry samples.

Funders	Funder number
Health~Holland, Top Sector Life Sciences & Health
Nierstichting	19OK005
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	091 501 61 81 01 36, 024.003.013

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

electrolyte transport
kidney
organoid
stem cells
tubuloid

Access to Document

10.1073/pnas.2216836120Licence: CC BY-NC-ND

pnas.2216836120Final published version, 8.56 MBLicence: CC BY-NC-ND

Cite this

Yengej, F. A. Y., Jansen, J., Ammerlaan, C. M. E., Dilmen, E., Casellas, C. P., Masereeuw, R., Hoenderop, J. G., Smeets, B., Rookmaaker, M. B., Verhaar, M. C., & Clevers, H. (2023). Tubuloid culture enables long-term expansion of functional human kidney tubule epithelium from iPSC-derived organoids. Proceedings of the National Academy of Sciences, 120(6), 1-11. Article e2216836120. https://doi.org/10.1073/pnas.2216836120

@article{aa422b91cbb24af28b847f7a504e41ad,

title = "Tubuloid culture enables long-term expansion of functional human kidney tubule epithelium from iPSC-derived organoids",

abstract = "Kidney organoids generated from induced pluripotent stem cells (iPSC) have proven valuable for studies of kidney development, disease, and therapeutic screening. However, specific applications have been hampered by limited expansion capacity, immaturity, off-target cells, and inability to access the apical side. Here, we apply recently developed tubuloid protocols to purify and propagate kidney epithelium from d7+18 (post nephrogenesis) iPSC-derived organoids. The resulting {\textquoteleft}iPSC organoid-derived (iPSCod){\textquoteright} tubuloids can be exponentially expanded for at least 2.5 mo, while retaining expression of important tubular transporters and segment-specific markers. This approach allows for selective propagation of the mature tubular epithelium, as immature cells, stroma, and undesirable off-target cells rapidly disappeared. iPSCod tubuloids provide easy apical access, which enabled functional evaluation and demonstration of essential secretion and electrolyte reabsorption processes. In conclusion, iPSCod tubuloids provide a different, complementary human kidney model that unlocks opportunities for functional characterization, disease modeling, and regenerative nephrology.",

keywords = "electrolyte transport, kidney, organoid, stem cells, tubuloid",

author = "Yengej, \{Fjodor A. Yousef\} and Jitske Jansen and Ammerlaan, \{Carola M. E.\} and Emre Dilmen and Casellas, \{Carla Pou\} and Rosalinde Masereeuw and Hoenderop, \{Joost G.\} and Bart Smeets and Rookmaaker, \{Maarten B.\} and Verhaar, \{Marianne C.\} and Hans Clevers",

note = "Publisher Copyright: Copyright {\textcopyright} 2023 the Author(s). Published by PNAS.",

year = "2023",

month = feb,

day = "7",

doi = "10.1073/pnas.2216836120",

language = "English",

volume = "120",

pages = "1--11",

journal = "Proceedings of the National Academy of Sciences",

issn = "1091-6490",

publisher = "National Academy of Sciences",

number = "6",

}

Yengej, FAY, Jansen, J, Ammerlaan, CME, Dilmen, E, Casellas, CP, Masereeuw, R, Hoenderop, JG, Smeets, B, Rookmaaker, MB, Verhaar, MC & Clevers, H 2023, 'Tubuloid culture enables long-term expansion of functional human kidney tubule epithelium from iPSC-derived organoids', Proceedings of the National Academy of Sciences, vol. 120, no. 6, e2216836120, pp. 1-11. https://doi.org/10.1073/pnas.2216836120

Tubuloid culture enables long-term expansion of functional human kidney tubule epithelium from iPSC-derived organoids. / Yengej, Fjodor A. Yousef; Jansen, Jitske; Ammerlaan, Carola M. E. et al.
In: Proceedings of the National Academy of Sciences, Vol. 120, No. 6, e2216836120, 07.02.2023, p. 1-11.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Tubuloid culture enables long-term expansion of functional human kidney tubule epithelium from iPSC-derived organoids

AU - Yengej, Fjodor A. Yousef

AU - Jansen, Jitske

AU - Ammerlaan, Carola M. E.

AU - Dilmen, Emre

AU - Casellas, Carla Pou

AU - Masereeuw, Rosalinde

AU - Hoenderop, Joost G.

AU - Smeets, Bart

AU - Rookmaaker, Maarten B.

AU - Verhaar, Marianne C.

AU - Clevers, Hans

PY - 2023/2/7

Y1 - 2023/2/7

N2 - Kidney organoids generated from induced pluripotent stem cells (iPSC) have proven valuable for studies of kidney development, disease, and therapeutic screening. However, specific applications have been hampered by limited expansion capacity, immaturity, off-target cells, and inability to access the apical side. Here, we apply recently developed tubuloid protocols to purify and propagate kidney epithelium from d7+18 (post nephrogenesis) iPSC-derived organoids. The resulting ‘iPSC organoid-derived (iPSCod)’ tubuloids can be exponentially expanded for at least 2.5 mo, while retaining expression of important tubular transporters and segment-specific markers. This approach allows for selective propagation of the mature tubular epithelium, as immature cells, stroma, and undesirable off-target cells rapidly disappeared. iPSCod tubuloids provide easy apical access, which enabled functional evaluation and demonstration of essential secretion and electrolyte reabsorption processes. In conclusion, iPSCod tubuloids provide a different, complementary human kidney model that unlocks opportunities for functional characterization, disease modeling, and regenerative nephrology.

AB - Kidney organoids generated from induced pluripotent stem cells (iPSC) have proven valuable for studies of kidney development, disease, and therapeutic screening. However, specific applications have been hampered by limited expansion capacity, immaturity, off-target cells, and inability to access the apical side. Here, we apply recently developed tubuloid protocols to purify and propagate kidney epithelium from d7+18 (post nephrogenesis) iPSC-derived organoids. The resulting ‘iPSC organoid-derived (iPSCod)’ tubuloids can be exponentially expanded for at least 2.5 mo, while retaining expression of important tubular transporters and segment-specific markers. This approach allows for selective propagation of the mature tubular epithelium, as immature cells, stroma, and undesirable off-target cells rapidly disappeared. iPSCod tubuloids provide easy apical access, which enabled functional evaluation and demonstration of essential secretion and electrolyte reabsorption processes. In conclusion, iPSCod tubuloids provide a different, complementary human kidney model that unlocks opportunities for functional characterization, disease modeling, and regenerative nephrology.

KW - electrolyte transport

KW - kidney

KW - organoid

KW - stem cells

KW - tubuloid

UR - https://www.scopus.com/pages/publications/85147808686

U2 - 10.1073/pnas.2216836120

DO - 10.1073/pnas.2216836120

M3 - Article

SN - 1091-6490

VL - 120

SP - 1

EP - 11

JO - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

IS - 6

M1 - e2216836120

ER -

Tubuloid culture enables long-term expansion of functional human kidney tubule epithelium from iPSC-derived organoids

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Cite this