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

Hubrecht Institute

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11 Citaten (Scopus)

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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.

Originele taal-2	Engels
Pagina's (van-tot)	e2216836120
Tijdschrift	Proceedings of the National Academy of Sciences of the United States of America
Volume	120
Nummer van het tijdschrift	6
DOI's	https://doi.org/10.1073/pnas.2216836120
Status	Gepubliceerd - 07 feb. 2023

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Yousef Yengej, F. A., Jansen, J., Ammerlaan, C. M. E., Dilmen, E., Pou Casellas, C., 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 of the United States of America, 120(6), e2216836120. https://doi.org/10.1073/pnas.2216836120

@article{e2c6717c81b44d5384594896fece3632,

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 '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.",

keywords = "Humans, Induced Pluripotent Stem Cells/metabolism, Kidney/metabolism, Epithelium, Organoids/metabolism, Kidney Tubules, Cell Differentiation",

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

year = "2023",

month = feb,

day = "7",

doi = "10.1073/pnas.2216836120",

language = "English",

volume = "120",

pages = "e2216836120",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "6",

}

Yousef Yengej, FA, Jansen, J, Ammerlaan, CME, Dilmen, E, Pou Casellas, C, 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 of the United States of America, vol. 120, nr. 6, blz. e2216836120. https://doi.org/10.1073/pnas.2216836120

Tubuloid culture enables long-term expansion of functional human kidney tubule epithelium from iPSC-derived organoids. / Yousef Yengej, Fjodor A; Jansen, Jitske; Ammerlaan, Carola M E et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 120, Nr. 6, 07.02.2023, blz. e2216836120.

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

TY - JOUR

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

AU - Yousef Yengej, Fjodor A

AU - Jansen, Jitske

AU - Ammerlaan, Carola M E

AU - Dilmen, Emre

AU - Pou Casellas, Carla

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 - Humans

KW - Induced Pluripotent Stem Cells/metabolism

KW - Kidney/metabolism

KW - Epithelium

KW - Organoids/metabolism

KW - Kidney Tubules

KW - Cell Differentiation

U2 - 10.1073/pnas.2216836120

DO - 10.1073/pnas.2216836120

M3 - Article

C2 - 36724260

SN - 0027-8424

VL - 120

SP - e2216836120

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 6

ER -

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

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