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 - Casellas, Carla Pou
AU - Masereeuw, Rosalinde
AU - Hoenderop, Joost G.
AU - Smeets, Bart
AU - Rookmaaker, Maarten B.
AU - Verhaar, Marianne C.
AU - Clevers, Hans
N1 - Funding Information:
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.
Publisher Copyright:
Copyright © 2023 the Author(s). Published by PNAS.
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 - http://www.scopus.com/inward/record.url?scp=85147808686&partnerID=8YFLogxK
U2 - 10.1073/pnas.2216836120
DO - 10.1073/pnas.2216836120
M3 - Article
C2 - 36724260
AN - SCOPUS:85147808686
SN - 0027-8424
VL - 120
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
M1 - e2216836120
ER -