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5. Certain heterozygous variants in the kinase domain of the serine/threonine kinase NEK8 can cause an autosomal dominant form of polycystic kidney disease

Author

Ambrose, John C., Arumugam, Prabhu, Bevers, Roel, Bleda, Marta, Boardman-Pretty, Freya, Boustred, Christopher R., Brittain, Helen, Caulfield, Mark J., Chan, Georgia C., Elgar, Greg, Fowler, Tom, Giess, Adam, Hamblin, Angela, Henderson, Shirley, Hubbard, Tim J.P., Jackson, Rob, Jones, Louise J., Kasperaviciute, Dalia, Kayikci, Melis, Kousathanas, Athanasios, Lahnstein, Lea, Leigh, Sarah E.A., Leong, Ivonne U.S., Lopez, Javier F., Maleady-Crowe, Fiona, McEntagart, Meriel, Minneci, Federico, Moutsianas, Loukas, Mueller, Michael, Murugaesu, Nirupa, Need, Anna C., O’Donovan, Peter, Odhams, Chris A., Patch, Christine, Pereira, Mariana Buongermino, Perez-Gil, Daniel, Pullinger, John, Rahim, Tahrima, Rendon, Augusto, Rogers, Tim, Savage, Kevin, Sawant, Kushmita, Scott, Richard H., Siddiq, Afshan, Sieghart, Alexander, Smith, Samuel C., Sosinsky, Alona, Stuckey, Alexander, Tanguy, Mélanie, Taylor Tavares, Ana Lisa, Thomas, Ellen R.A., Thompson, Simon R., Tucci, Arianna, Welland, Matthew J., Williams, Eleanor, Witkowska, Katarzyna, Wood, Suzanne M., Claus, Laura R., Chen, Chuan, Stallworth, Jennifer, Turner, Joshua L., Slaats, Gisela G., Hawks, Alexandra L., Mabillard, Holly, Senum, Sarah R., Srikanth, Sujata, Flanagan-Steet, Heather, Louie, Raymond J., Silver, Josh, Lerner-Ellis, Jordan, Morel, Chantal, Mighton, Chloe, Sleutels, Frank, van Slegtenhorst, Marjon, van Ham, Tjakko, Brooks, Alice S., Dorresteijn, Eiske M., Barakat, Tahsin Stefan, Dahan, Karin, Demoulin, Nathalie, Goffin, Eric Jean, Olinger, Eric, Larsen, Martin, Hertz, Jens Michael, Lilien, Marc R., Obeidová, Lena, Seeman, Tomas, Stone, Hillarey K., Kerecuk, Larissa, Gurgu, Mihai, Yousef Yengej, Fjodor A., Ammerlaan, Carola M.E., Rookmaaker, Maarten B., Hanna, Christian, Rogers, R. Curtis, Duran, Karen, Peters, Edith, Sayer, John A., van Haaften, Gijs, Harris, Peter C., Ling, Kun, Mason, Jennifer M., van Eerde, Albertien M., and Steet, Richard

Published
2023
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9. Discrepancies between transcutaneous and estimated glomerular filtration rates in rats with chronic kidney disease

Author

Nefro Vasculaire Geneeskunde, Regenerative Medicine and Stem Cells, Circulatory Health, MS Nefrologie, Pieters, Tobias T, Besseling, Paul J, Bovée, Dominique M, Rookmaaker, Maarten B, Verhaar, Marianne C, Yard, Benito, Hoorn, Ewout J, Joles, Jaap A, Nefro Vasculaire Geneeskunde, Regenerative Medicine and Stem Cells, Circulatory Health, MS Nefrologie, Pieters, Tobias T, Besseling, Paul J, Bovée, Dominique M, Rookmaaker, Maarten B, Verhaar, Marianne C, Yard, Benito, Hoorn, Ewout J, and Joles, Jaap A

Published
2024

10. Tubuloid differentiation to model the human distal nephron and collecting duct in health and disease

Author

Nefro Vasculaire Geneeskunde, AIOS Psychiatrie, Regenerative Medicine and Stem Cells, Circulatory Health, Cancer, CMM, Hubrecht Institute with UMC, Yousef Yengej, Fjodor A, Pou Casellas, Carla, Ammerlaan, Carola M E, Olde Hanhof, Charlotte J A, Dilmen, Emre, Beumer, Joep, Begthel, Harry, Meeder, Elise M G, Hoenderop, Joost G, Rookmaaker, Maarten B, Verhaar, Marianne C, Clevers, Hans, Nefro Vasculaire Geneeskunde, AIOS Psychiatrie, Regenerative Medicine and Stem Cells, Circulatory Health, Cancer, CMM, Hubrecht Institute with UMC, Yousef Yengej, Fjodor A, Pou Casellas, Carla, Ammerlaan, Carola M E, Olde Hanhof, Charlotte J A, Dilmen, Emre, Beumer, Joep, Begthel, Harry, Meeder, Elise M G, Hoenderop, Joost G, Rookmaaker, Maarten B, Verhaar, Marianne C, and Clevers, Hans

Published
2024

15. Cysteamine–bicalutamide combination therapy corrects proximal tubule phenotype in cystinosis

Author

Jamalpoor, Amer, van Gelder, Charlotte AGH, Yousef Yengej, Fjodor A, Zaal, Esther A, Berlingerio, Sante P, Veys, Koenraad R, Pou Casellas, Carla, Voskuil, Koen, Essa, Khaled, Ammerlaan, Carola ME, Rega, Laura Rita, van der Welle, Reini EN, Lilien, Marc R, Rookmaaker, Maarten B, Clevers, Hans, Klumperman, Judith, Levtchenko, Elena, Berkers, Celia R, Verhaar, Marianne C, Altelaar, Maarten, Masereeuw, Rosalinde, and Janssen, Manoe J

Published
2021
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16. Certain heterozygous variants in the kinase domain of the serine/threonine kinase NEK8 can cause an autosomal dominant form of polycystic kidney disease

Author

Claus, Laura R., primary, Chen, Chuan, additional, Stallworth, Jennifer, additional, Turner, Joshua L., additional, Slaats, Gisela G., additional, Hawks, Alexandra L., additional, Mabillard, Holly, additional, Senum, Sarah R., additional, Srikanth, Sujata, additional, Flanagan-Steet, Heather, additional, Louie, Raymond J., additional, Silver, Josh, additional, Lerner-Ellis, Jordan, additional, Morel, Chantal, additional, Mighton, Chloe, additional, Sleutels, Frank, additional, van Slegtenhorst, Marjon, additional, van Ham, Tjakko, additional, Brooks, Alice S., additional, Dorresteijn, Eiske M., additional, Barakat, Tahsin Stefan, additional, Dahan, Karin, additional, Demoulin, Nathalie, additional, Goffin, Eric Jean, additional, Olinger, Eric, additional, Larsen, Martin, additional, Hertz, Jens Michael, additional, Lilien, Marc R., additional, Obeidová, Lena, additional, Seeman, Tomas, additional, Stone, Hillarey K., additional, Kerecuk, Larissa, additional, Gurgu, Mihai, additional, Yousef Yengej, Fjodor A., additional, Ammerlaan, Carola M.E., additional, Rookmaaker, Maarten B., additional, Hanna, Christian, additional, Rogers, R. Curtis, additional, Duran, Karen, additional, Peters, Edith, additional, Sayer, John A., additional, van Haaften, Gijs, additional, Harris, Peter C., additional, Ling, Kun, additional, Mason, Jennifer M., additional, van Eerde, Albertien M., additional, Steet, Richard, additional, Ambrose, John C., additional, Arumugam, Prabhu, additional, Bevers, Roel, additional, Bleda, Marta, additional, Boardman-Pretty, Freya, additional, Boustred, Christopher R., additional, Brittain, Helen, additional, Caulfield, Mark J., additional, Chan, Georgia C., additional, Elgar, Greg, additional, Fowler, Tom, additional, Giess, Adam, additional, Hamblin, Angela, additional, Henderson, Shirley, additional, Hubbard, Tim J.P., additional, Jackson, Rob, additional, Jones, Louise J., additional, Kasperaviciute, Dalia, additional, Kayikci, Melis, additional, Kousathanas, Athanasios, additional, Lahnstein, Lea, additional, Leigh, Sarah E.A., additional, Leong, Ivonne U.S., additional, Lopez, Javier F., additional, Maleady-Crowe, Fiona, additional, McEntagart, Meriel, additional, Minneci, Federico, additional, Moutsianas, Loukas, additional, Mueller, Michael, additional, Murugaesu, Nirupa, additional, Need, Anna C., additional, O’Donovan, Peter, additional, Odhams, Chris A., additional, Patch, Christine, additional, Pereira, Mariana Buongermino, additional, Perez-Gil, Daniel, additional, Pullinger, John, additional, Rahim, Tahrima, additional, Rendon, Augusto, additional, Rogers, Tim, additional, Savage, Kevin, additional, Sawant, Kushmita, additional, Scott, Richard H., additional, Siddiq, Afshan, additional, Sieghart, Alexander, additional, Smith, Samuel C., additional, Sosinsky, Alona, additional, Stuckey, Alexander, additional, Tanguy, Mélanie, additional, Taylor Tavares, Ana Lisa, additional, Thomas, Ellen R.A., additional, Thompson, Simon R., additional, Tucci, Arianna, additional, Welland, Matthew J., additional, Williams, Eleanor, additional, Witkowska, Katarzyna, additional, and Wood, Suzanne M., additional

Published
2023
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17. Tubuloids derived from human adult kidney and urine for personalized disease modeling

Author

Schutgens, Frans, Rookmaaker, Maarten B, Margaritis, Thanasis, Rios, Anne, Ammerlaan, Carola, Jansen, Jitske, Gijzen, Linda, Vormann, Marianne, Vonk, Annelotte, Viveen, Marco, Yengej, Fjodor Yousef, Derakhshan, Sepide, de Winter-de Groot, Karin M., Artegiani, Benedetta, van Boxtel, Ruben, Cuppen, Edwin, Hendrickx, Antoni P. A., van den Heuvel-Eibrink, Marry M., Heitzer, Ellen, Lanz, Henriette, Beekman, Jeffrey, Murk, Jean-Luc, Masereeuw, Rosalinde, Holstege, Frank, Drost, Jarno, Verhaar, Marianne C, and Clevers, Hans

Published
2019
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19. Tubuloid culture enables long-term expansion of functional human kidney tubule epithelium from iPSC-derived organoids

Author

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

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.

Published
2023

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

Author

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

Published
2023

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

Author

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

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.

Published
2023

22. Author Correction: Transcriptomic profile comparison reveals conservation of ionocytes across multiple organs

Author

Nefro Vasculaire Geneeskunde, Circulatory Health, Regenerative Medicine and Stem Cells, Cancer, CMM, Hubrecht Institute with UMC, Pou Casellas, Carla, Pleguezuelos-Manzano, Cayetano, Rookmaaker, Maarten B, Verhaar, Marianne C, Clevers, Hans, Nefro Vasculaire Geneeskunde, Circulatory Health, Regenerative Medicine and Stem Cells, Cancer, CMM, Hubrecht Institute with UMC, Pou Casellas, Carla, Pleguezuelos-Manzano, Cayetano, Rookmaaker, Maarten B, Verhaar, Marianne C, and Clevers, Hans

Published
2023

23. Transcriptomic profile comparison reveals conservation of ionocytes across multiple organs

Author

Nefro Vasculaire Geneeskunde, MS Nefrologie, Regenerative Medicine and Stem Cells, Circulatory Health, CMM, Cancer, Hubrecht Institute with UMC, Pou Casellas, Carla, Pleguezuelos-Manzano, Cayetano, Rookmaaker, Maarten B., Verhaar, Marianne C., Clevers, Hans, Nefro Vasculaire Geneeskunde, MS Nefrologie, Regenerative Medicine and Stem Cells, Circulatory Health, CMM, Cancer, Hubrecht Institute with UMC, Pou Casellas, Carla, Pleguezuelos-Manzano, Cayetano, Rookmaaker, Maarten B., Verhaar, Marianne C., and Clevers, Hans

Published
2023

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

Author

Nefro Vasculaire Geneeskunde, MS Nefrologie, Regenerative Medicine and Stem Cells, Circulatory Health, CMM, Cancer, Hubrecht Institute with UMC, Yousef Yengej, Fjodor A., Jansen, Jitske, Ammerlaan, Carola M.E., Dilmen, Emre, Casellas, Carla Pou, Masereeuw, Rosalinde, Hoenderop, Joost G., Smeets, Bart, Rookmaaker, Maarten B., Verhaar, Marianne C., Clevers, Hans, Nefro Vasculaire Geneeskunde, MS Nefrologie, Regenerative Medicine and Stem Cells, Circulatory Health, CMM, Cancer, Hubrecht Institute with UMC, Yousef Yengej, Fjodor A., Jansen, Jitske, Ammerlaan, Carola M.E., Dilmen, Emre, Casellas, Carla Pou, Masereeuw, Rosalinde, Hoenderop, Joost G., Smeets, Bart, Rookmaaker, Maarten B., Verhaar, Marianne C., and Clevers, Hans

Published
2023

26. Parathyroid hormone and phosphate homeostasis in patients with Bartter and Gitelman syndrome: an international cross-sectional study

Author

Verploegen, Maartje F A, Vargas-Poussou, Rosa, Walsh, Stephen B, Alpay, Harika, Amouzegar, Atefeh, Ariceta Iraola, Gema, Atmis, Bahriye, Bacchetta, Justine, Bárány, Peter, Baron, Stéphanie, Bayrakci, Umut Selda, Belge, Hendrica, Besouw, Martine, Blanchard, Anne, Bökenkamp, Arend, Boyer, Olivia, Burgmaier, Kathrin, Calò, Lorenzo A, Decramer, Stéphane, Devuyst, Olivier, van Dyck, Maria, Ferraro, Pietro Manuel, Fila, Marc, Francisco, Telma, Ghiggeri, Gian Marco, Gondra, Leire, Guarino, Stefano, Hooman, Nakysa, Hoorn, Ewout J, Houillier, Pascal, Kamperis, Konstantinos, Kari, Jameela A, Konrad, Martin, Levtchenko, Elena, Lucchetti, Laura, Lugani, Francesca, Marzuillo, Pierluigi, Mohidin, Barian, Neuhaus, Thomas J, Osman, Abdaldafae, Papizh, Svetlana, Perelló, Manel, Rookmaaker, Maarten B, Conti, Valerie Said, Santos, Fernando, Sawaf, Ghalia, Serdaroglu, Erkin, Szczepanska, Maria, Taroni, Francesca, Topaloglu, Rezan, Trepiccione, Francesco, Vidal, Enrico, Wan, Elizabeth R, Weber, Lutz, Yildirim, Zeynep Yuruk, Yüksel, Selçuk, Zlatanova, Galia, Bockenhauer, Detlef, Emma, Francesco, Nijenhuis, Tom, Universitat Autònoma de Barcelona, Institut Català de la Salut, [Verploegen MFA] Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands. [Vargas-Poussou R] Department of Genetics, Centre de Références MARHEA, Hôpital Européen Georges Pompidou Assistance Publique Hôpitaux de Paris, Paris, France. [Walsh SB] Department of Renal Medicine, University College London, London, UK. [Alpay H] Division of Paediatric Nephrology, Faculty of Medicine, Marmara University, Istanbul, Turkey. [Amouzegar A] Division of Nephrology, Department of Medicine, Firoozgar Clinical Research Development Center, Iran University of Medical Sciences, Tehran, Iran. [Ariceta G] Servei de Nefrologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Perelló M] Servei de Nefrologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, Verploegen M. F. A., Vargas-Poussou R., Walsh S. B., ALPAY H., Amouzegar A., Ariceta G., ATMIŞ B., Bacchetta J., Barany P., Baron S., et al., Verploegen, Maartje F A, Vargas-Poussou, Rosa, Walsh, Stephen B, Alpay, Harika, Amouzegar, Atefeh, Ariceta, Gema, Atmis, Bahriye, Bacchetta, Justine, Bárány, Peter, Baron, Stéphanie, Bayrakci, Umut Selda, Belge, Hendrica, Besouw, Martine, Blanchard, Anne, Bökenkamp, Arend, Boyer, Olivia, Burgmaier, Kathrin, Calò, Lorenzo A, Decramer, Stéphane, Devuyst, Olivier, van Dyck, Maria, Ferraro, Pietro Manuel, Fila, Marc, Francisco, Telma, Ghiggeri, Gian Marco, Gondra, Leire, Guarino, Stefano, Hooman, Nakysa, Hoorn, Ewout J, Houillier, Pascal, Kamperis, Konstantino, Kari, Jameela A, Konrad, Martin, Levtchenko, Elena, Lucchetti, Laura, Lugani, Francesca, Marzuillo, Pierluigi, Mohidin, Barian, Neuhaus, Thomas J, Osman, Abdaldafae, Papizh, Svetlana, Perelló, Manel, Rookmaaker, Maarten B, Conti, Valerie Said, Santos, Fernando, Sawaf, Ghalia, Serdaroglu, Erkin, Szczepanska, Maria, Taroni, Francesca, Topaloglu, Rezan, Trepiccione, Francesco, Vidal, Enrico, Wan, Elizabeth R, Weber, Lutz, Yildirim, Zeynep Yuruk, Yüksel, Selçuk, Zlatanova, Galia, Bockenhauer, Detlef, Emma, Francesco, Nijenhuis, Tom, and UCL - SSS/IREC/NEFR - Pôle de Néphrologie

Subjects
Internal Diseases, Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Parathyroid Hormone [CHEMICALS AND DRUGS], Homeòstasi, urologic and male genital diseases, Sağlık Bilimleri, İç Hastalıkları, Clinical Medicine (MED), Bartter syndomr, Transplantasyon, Gitelman Syndrome/complications, salt losing tubulopathies, Homeostasis, HYPERCALCIURIA, Klinik Tıp (MED), Child, enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales::defectos congénitos del transporte tubular renal::síndrome de Gitelman [ENFERMEDADES], Klinik Tıp, Hyperparathyroidism, Tıp, Nefroloji, fenómenos fisiológicos::homeostasis [FENÓMENOS Y PROCESOS], Nephrology, Üroloji, Medicine, Gitelman syndrome, Ronyons - Malalties - Malformacions, Urology, CALCIUM, Phosphates, UROLOGY & NEPHROLOGY, Health Sciences, Humans, parathyroid hormone, HYPERPARATHYROIDISM, ÜROLOJİ VE NEFROLOJİ, hormonas, sustitutos de hormonas y antagonistas de hormonas::hormonas::hormonas peptídicas::hormona paratiroidea [COMPUESTOS QUÍMICOS Y DROGAS], phosphate, Transplantation, Internal Medicine Sciences, Male Urogenital Diseases::Urologic Diseases::Kidney Diseases::Renal Tubular Transport, Inborn Errors::Bartter Syndrome [DISEASES], Dahili Tıp Bilimleri, Hormones peptídiques, CLINICAL MEDICINE, GENE, Bartter syndrome, Male Urogenital Diseases::Urologic Diseases::Kidney Diseases::Renal Tubular Transport, Inborn Errors::Gitelman Syndrome [DISEASES], Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Cross-Sectional Studies, Calcium, Bartter Syndrome/complications, Physiological Phenomena::Homeostasis [PHENOMENA AND PROCESSES], enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales::defectos congénitos del transporte tubular renal::síndrome de Bartter [ENFERMEDADES]
Abstract

European Reference Network for Rare Kidney Diseases (ERKNet) - European Union; Dutch Kidney Foundation [19OI06], Verploegen MFA, Vargas-Poussou R, Walsh SB, Alpay H, Amouzegar A, Ariceta G, Atmis B, Bacchetta J, Bárány P, Baron S, Bayrakci US, Belge H, Besouw M, Blanchard A, Bökenkamp A, Boyer O, Burgmaier K, Calò LA, Decramer S, Devuyst O, van Dyck M, Ferraro PM, Fila M, Francisco T, Ghiggeri GM, Gondra L, Guarino S, Hooman N, Hoorn EJ, Houillier P, Kamperis K, Kari JA, Konrad M, Levtchenko E, Lucchetti L, Lugani F, Marzuillo P, Mohidin B, Neuhaus TJ, Osman A, Papizh S, Perelló M, Rookmaaker MB, Conti VS, Santos F, Sawaf G, Serdaroglu E, Szczepanska M, Taroni F, Topaloglu R, Trepiccione F, Vidal E, Wan ER, Weber L, Yildirim ZY, Yüksel S, Zlatanova G, Bockenhauer D, Emma F, Nijenhuis T

Published
2022
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27. Optimizing carboplatin dosing by an improved prediction of carboplatin clearance using a CT‐enhanced estimate of renal function.

Author

Molenaar‐Kuijsten, Laura, Pieters, Tobias T., Veldhuis, Wouter B., Moeskops, Pim, Rijkhorst, Erik Jan, Dorlo, Thomas P. C., Beijnen, Jos H., Steeghs, Neeltje, Rookmaaker, Maarten B., and Huitema, Alwin D. R.

Subjects
KIDNEY physiology, CARBOPLATIN, GLOMERULAR filtration rate, BODY composition
Abstract

Aims: Carboplatin is generally dosed based on a modified Calvert formula, in which the Cockcroft–Gault‐based creatinine clearance (CRCL) is used as proxy for the glomerular filtration rate (GFR). The Cockcroft–Gault formula (CG) overpredicts CRCL in patients with an aberrant body composition. The CT‐enhanced estimate of RenAl FuncTion (CRAFT) was developed to compensate for this overprediction. We aimed to evaluate whether carboplatin clearance is better predicted by CRCL based on the CRAFT compared to the CG. Methods: Data of four previously conducted trials was used. The CRAFT was divided by serum creatinine to derive CRCL. The difference between CRAFT‐ and CG‐based CRCL was assessed by population pharmacokinetic modelling. Furthermore, the difference in calculated carboplatin dose was assessed in a heterogeneous dataset. Results: In total, 108 patients were included in the analysis. Addition of the CRAFT‐ and CG‐based CRCL as covariate on carboplatin clearance led, respectively, to an improved model fit with a 26‐point drop in objective function value and a worsened model fit with an increase of 8 points. In 19 subjects with serum creatinine <50 μmol/L, the calculated carboplatin dose was 233 mg higher using the CG. Conclusions: Carboplatin clearance is better predicted by CRAFT vs. CG‐based CRCL. In subjects with low serum creatinine, the calculated carboplatin dose using CG exceeds the dose using CRAFT, which might explain the need for dose capping when using the CG. Therefore, the CRAFT might be an alternative for dose capping while still dosing accurately. [ABSTRACT FROM AUTHOR]

Published
2023
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28. Tubuloid culture enables long-term expansion of functional human kidney tubule epithelium from iPSC-derived organoids

Author

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

Published
2023
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31. Regulation of Solute Carriers OCT2 and OAT1/3 in the Kidney: A Phylogenetic, Ontogenetic and Cell Dynamic Perspective

Author

Pou Casellas, Carla, Jansen, Katja, Rookmaaker, Maarten B, Clevers, Hans, Verhaar, Marianne C, Masereeuw, Rosalinde, Pou Casellas, Carla, Jansen, Katja, Rookmaaker, Maarten B, Clevers, Hans, Verhaar, Marianne C, and Masereeuw, Rosalinde

Abstract

Over the course of more than 500 million years, the kidneys have undergone a remarkable evolution from primitive nephric tubes to intricate filtration-reabsorption systems that maintain homeostasis and remove metabolic end products from the body. The evolutionarily conserved solute carriers organic cation transporter 2 (OCT2) and organic anion transporters 1 and 3 (OAT1/3) coordinate the active secretion of a broad range of endogenous and exogenous substances, many of which accumulate in the blood of patients with kidney failure despite dialysis. Harnessing OCT2 and OAT1/3 through functional preservation or regeneration could alleviate the progression of kidney disease. Additionally, it would improve current in vitro test models that lose their expression in culture. With this review, we explore OCT2 and OAT1/3 regulation from different perspectives: phylogenetic, ontogenetic, and cell dynamic. Our aim is to identify possible molecular targets both to help prevent or compen-sate for the loss of transport activity in patients with kidney disease and to enable endogenous OCT2 and OAT1/3 induction in vitro in order to develop better models for drug development.

Published
2022

32. Parathyroid hormone and phosphate homeostasis in patients with Bartter and Gitelman syndrome: an international cross-sectional study

Author

MS Nefrologie, Regenerative Medicine and Stem Cells, Verploegen, Maartje F.A., Vargas-Poussou, Rosa, Walsh, Stephen B., Alpay, Harika, Amouzegar, Atefeh, Ariceta, Gema, Atmis, Bahriye, Bacchetta, Justine, Bárány, Peter, Baron, Stéphanie, Bayrakci, Umut Selda, Belge, Hendrica, Besouw, Martine, Blanchard, Anne, Bökenkamp, Arend, Boyer, Olivia, Burgmaier, Kathrin, Calò, Lorenzo A., Decramer, Stéphane, Devuyst, Olivier, van Dyck, Maria, Ferraro, Pietro Manuel, Fila, Marc, Francisco, Telma, Ghiggeri, Gian Marco, Gondra, Leire, Guarino, Stefano, Hooman, Nakysa, Hoorn, Ewout J., Houillier, Pascal, Kamperis, Konstantinos, Kari, Jameela A., Konrad, Martin, Levtchenko, Elena, Lucchetti, Laura, Lugani, Francesca, Marzuillo, Pierluigi, Mohidin, Barian, Neuhaus, Thomas J., Osman, Abdaldafae, Papizh, Svetlana, Perelló, Manel, Rookmaaker, Maarten B., Conti, Valerie Said, Santos, Fernando, Sawaf, Ghalia, Serdaroglu, Erkin, Szczepanska, Maria, Taroni, Francesca, Topaloglu, Rezan, Trepiccione, Francesco, Vidal, Enrico, Wan, Elizabeth R., Weber, Lutz, Yildirim, Zeynep Yuruk, Yüksel, Selçuk, Zlatanova, Galia, Bockenhauer, Detlef, Emma, Francesco, Nijenhuis, Tom, MS Nefrologie, Regenerative Medicine and Stem Cells, Verploegen, Maartje F.A., Vargas-Poussou, Rosa, Walsh, Stephen B., Alpay, Harika, Amouzegar, Atefeh, Ariceta, Gema, Atmis, Bahriye, Bacchetta, Justine, Bárány, Peter, Baron, Stéphanie, Bayrakci, Umut Selda, Belge, Hendrica, Besouw, Martine, Blanchard, Anne, Bökenkamp, Arend, Boyer, Olivia, Burgmaier, Kathrin, Calò, Lorenzo A., Decramer, Stéphane, Devuyst, Olivier, van Dyck, Maria, Ferraro, Pietro Manuel, Fila, Marc, Francisco, Telma, Ghiggeri, Gian Marco, Gondra, Leire, Guarino, Stefano, Hooman, Nakysa, Hoorn, Ewout J., Houillier, Pascal, Kamperis, Konstantinos, Kari, Jameela A., Konrad, Martin, Levtchenko, Elena, Lucchetti, Laura, Lugani, Francesca, Marzuillo, Pierluigi, Mohidin, Barian, Neuhaus, Thomas J., Osman, Abdaldafae, Papizh, Svetlana, Perelló, Manel, Rookmaaker, Maarten B., Conti, Valerie Said, Santos, Fernando, Sawaf, Ghalia, Serdaroglu, Erkin, Szczepanska, Maria, Taroni, Francesca, Topaloglu, Rezan, Trepiccione, Francesco, Vidal, Enrico, Wan, Elizabeth R., Weber, Lutz, Yildirim, Zeynep Yuruk, Yüksel, Selçuk, Zlatanova, Galia, Bockenhauer, Detlef, Emma, Francesco, and Nijenhuis, Tom

Published
2022

33. Parathyroid hormone and phosphate homeostasis in patients with Bartter and Gitelman syndrome:an international cross-sectional study

Author

Verploegen, Maartje F.A., Vargas-Poussou, Rosa, Walsh, Stephen B., Alpay, Harika, Amouzegar, Atefeh, Ariceta, Gema, Atmis, Bahriye, Bacchetta, Justine, Bárány, Peter, Baron, Stéphanie, Bayrakci, Umut Selda, Belge, Hendrica, Besouw, Martine, Blanchard, Anne, Bökenkamp, Arend, Boyer, Olivia, Burgmaier, Kathrin, Calò, Lorenzo A., Decramer, Stéphane, Devuyst, Olivier, van Dyck, Maria, Ferraro, Pietro Manuel, Fila, Marc, Francisco, Telma, Ghiggeri, Gian Marco, Gondra, Leire, Guarino, Stefano, Hooman, Nakysa, Hoorn, Ewout J., Houillier, Pascal, Kamperis, Konstantinos, Kari, Jameela A., Konrad, Martin, Levtchenko, Elena, Lucchetti, Laura, Lugani, Francesca, Marzuillo, Pierluigi, Mohidin, Barian, Neuhaus, Thomas J., Osman, Abdaldafae, Papizh, Svetlana, Perelló, Manel, Rookmaaker, Maarten B., Conti, Valerie Said, Santos, Fernando, Sawaf, Ghalia, Serdaroglu, Erkin, Szczepanska, Maria, Taroni, Francesca, Topaloglu, Rezan, Trepiccione, Francesco, Vidal, Enrico, Wan, Elizabeth R., Weber, Lutz, Yildirim, Zeynep Yuruk, Yüksel, Selçuk, Zlatanova, Galia, Bockenhauer, Detlef, Emma, Francesco, Nijenhuis, Tom, Verploegen, Maartje F.A., Vargas-Poussou, Rosa, Walsh, Stephen B., Alpay, Harika, Amouzegar, Atefeh, Ariceta, Gema, Atmis, Bahriye, Bacchetta, Justine, Bárány, Peter, Baron, Stéphanie, Bayrakci, Umut Selda, Belge, Hendrica, Besouw, Martine, Blanchard, Anne, Bökenkamp, Arend, Boyer, Olivia, Burgmaier, Kathrin, Calò, Lorenzo A., Decramer, Stéphane, Devuyst, Olivier, van Dyck, Maria, Ferraro, Pietro Manuel, Fila, Marc, Francisco, Telma, Ghiggeri, Gian Marco, Gondra, Leire, Guarino, Stefano, Hooman, Nakysa, Hoorn, Ewout J., Houillier, Pascal, Kamperis, Konstantinos, Kari, Jameela A., Konrad, Martin, Levtchenko, Elena, Lucchetti, Laura, Lugani, Francesca, Marzuillo, Pierluigi, Mohidin, Barian, Neuhaus, Thomas J., Osman, Abdaldafae, Papizh, Svetlana, Perelló, Manel, Rookmaaker, Maarten B., Conti, Valerie Said, Santos, Fernando, Sawaf, Ghalia, Serdaroglu, Erkin, Szczepanska, Maria, Taroni, Francesca, Topaloglu, Rezan, Trepiccione, Francesco, Vidal, Enrico, Wan, Elizabeth R., Weber, Lutz, Yildirim, Zeynep Yuruk, Yüksel, Selçuk, Zlatanova, Galia, Bockenhauer, Detlef, Emma, Francesco, and Nijenhuis, Tom

Abstract

Background:Small cohort studies have reported high parathyroid hormone (PTH) levels in patients with Bartter syndrome and lower serum phosphate levels have anecdotally been reported in patients with Gitelman syndrome. In this cross-sectional study, we assessed PTH and phosphate homeostasis in a large cohort of patients with salt-losing tubulopathies. Methods:Clinical and laboratory data of 589 patients with Bartter and Gitelman syndrome were provided by members of the European Rare Kidney Diseases Reference Network (ERKNet) and the European Society for Paediatric Nephrology (ESPN). Results:A total of 285 patients with Bartter syndrome and 304 patients with Gitelman syndrome were included for analysis. Patients with Bartter syndrome type I and II had the highest median PTH level (7.5 pmol/L) and 56% had hyperparathyroidism (PTH >7.0 pmol/L). Serum calcium was slightly lower in Bartter syndrome type I and II patients with hyperparathyroidism (2.42 versus 2.49 mmol/L; P = .038) compared to those with normal PTH levels and correlated inversely with PTH (rs −0.253; P = .009). Serum phosphate and urinary phosphate excretion did not correlate with PTH. Overall, 22% of patients had low serum phosphate levels (phosphate—standard deviation score < −2), with the highest prevalence in patients with Bartter syndrome type III (32%). Serum phosphate correlated with tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) (rs 0.699; P < .001), suggesting renal phosphate wasting. Conclusions:Hyperparathyroidism is frequent in patients with Bartter syndrome type I and II. Low serum phosphate is observed in a significant number of patients with Bartter and Gitelman syndrome and appears associated with renal phosphate wasting.

Published
2022

34. Substrate Stiffness Determines the Establishment of Apical-Basal Polarization in Renal Epithelial Cells but Not in Tubuloid-Derived Cells

Author

Hagelaars, Maria J., Yousef Yengej, Fjodor A., Verhaar, Marianne C., Rookmaaker, Maarten B., Loerakker, Sandra, Bouten, Carlijn V.C., Hagelaars, Maria J., Yousef Yengej, Fjodor A., Verhaar, Marianne C., Rookmaaker, Maarten B., Loerakker, Sandra, and Bouten, Carlijn V.C.

Abstract

Mechanical guidance of tissue morphogenesis is an emerging method of regenerative medicine that can be employed to steer functional kidney architecture for the purpose of bioartificial kidney design or renal tissue engineering strategies. In kidney morphogenesis, apical-basal polarization of renal epithelial cells is paramount for tubule formation and subsequent tissue functions like excretion and resorption. In kidney epithelium, polarization is initiated by integrin-mediated cell-matrix adhesion at the cell membrane. Cellular mechanobiology research has indicated that this integrin-mediated adhesion is responsive to matrix stiffness, raising the possibility to use matrix stiffness as a handle to steer cell polarization. Herein, we evaluate apical-basal polarization in response to 2D substates of different stiffness (1, 10, 50 kPa and glass) in Madin Darby Canine Kidney cells (MDCKs), a classic canine-derived cell model of epithelial polarization, and in tubuloid-derived cells, established from human primary cells derived from adult kidney tissue. Our results show that sub-physiological (1 kPa) substrate stiffness with low integrin-based adhesion induces polarization in MDCKs, while MDCKs on supraphysiological (>10 kPa) stiffness remain unpolarized. Inhibition of integrin, indeed, allows for polarization on the supraphysiological substrates, suggesting that increased cellular adhesion on stiff substrates opposes polarization. In contrast, tubuloid-derived cells do not establish apical-basal polarization on 2D substrates, irrespective of substrate stiffness, despite their ability to polarize in 3D environments. Further analysis implies that the 2D cultured tubuloid-derived cells have a diminished mechanosensitive capacity when presented with different substrate stiffnesses due to immature focal adhesions and the absence of a connection between focal adhesions and the cytoskeleton. Overall, this study demonstrates that apical-basal polarization is a complex pro

Published
2022

37. Parathyroid hormone and phosphate homeostasis in patients with Bartter and Gitelman syndrome: an international cross-sectional study

Author

Verploegen, Maartje F. A., Vargas-Poussou, Rosa, Walsh, Stephen B., Alpay, Harika, Amouzegar, Atefeh, Ariceta, Gema, Atmis, Bahriye, Bacchetta, Justine, Barany, Peter, Baron, Stephanie, Bayrakci, Umut Selda, Belge, Hendrica, Besouw, Martine, Blanchard, Anne, Bokenkamp, Arend, Boyer, Olivia, Burgmaier, Kathrin, Calo, Lorenzo A., Decramer, Stephane, Devuyst, Olivier, van Dyck, Maria, Ferraro, Pietro Manuel, Fila, Marc, Francisco, Telma, Ghiggeri, Gian Marco, Gondra, Leire, Guarino, Stefano, Hooman, Nakysa, Hoorn, Ewout J., Houillier, Pascal, Kamperis, Konstantinos, Kari, Jameela A., Konrad, Martin, Levtchenko, Elena, Lucchetti, Laura, Lugani, Francesca, Marzuillo, Pierluigi, Mohidin, Barian, Neuhaus, Thomas J., Osman, Abdaldafae, Papizh, Svetlana, Perello, Manel, Rookmaaker, Maarten B., Conti, Valerie Said, Santos, Fernando, Sawaf, Ghalia, Serdaroglu, Erkin, Szczepanska, Maria, Taroni, Francesca, Topaloglu, Rezan, Trepiccione, Francesco, Vidal, Enrico, Wan, Elizabeth R., Weber, Lutz, Yildirim, Zeynep Yuruk, Yuksel, Selcuk, Zlatanova, Galia, Bockenhauer, Detlef, Emma, Francesco, Nijenhuis, Tom, Verploegen, Maartje F. A., Vargas-Poussou, Rosa, Walsh, Stephen B., Alpay, Harika, Amouzegar, Atefeh, Ariceta, Gema, Atmis, Bahriye, Bacchetta, Justine, Barany, Peter, Baron, Stephanie, Bayrakci, Umut Selda, Belge, Hendrica, Besouw, Martine, Blanchard, Anne, Bokenkamp, Arend, Boyer, Olivia, Burgmaier, Kathrin, Calo, Lorenzo A., Decramer, Stephane, Devuyst, Olivier, van Dyck, Maria, Ferraro, Pietro Manuel, Fila, Marc, Francisco, Telma, Ghiggeri, Gian Marco, Gondra, Leire, Guarino, Stefano, Hooman, Nakysa, Hoorn, Ewout J., Houillier, Pascal, Kamperis, Konstantinos, Kari, Jameela A., Konrad, Martin, Levtchenko, Elena, Lucchetti, Laura, Lugani, Francesca, Marzuillo, Pierluigi, Mohidin, Barian, Neuhaus, Thomas J., Osman, Abdaldafae, Papizh, Svetlana, Perello, Manel, Rookmaaker, Maarten B., Conti, Valerie Said, Santos, Fernando, Sawaf, Ghalia, Serdaroglu, Erkin, Szczepanska, Maria, Taroni, Francesca, Topaloglu, Rezan, Trepiccione, Francesco, Vidal, Enrico, Wan, Elizabeth R., Weber, Lutz, Yildirim, Zeynep Yuruk, Yuksel, Selcuk, Zlatanova, Galia, Bockenhauer, Detlef, Emma, Francesco, and Nijenhuis, Tom

Abstract

Background Small cohort studies have reported high parathyroid hormone (PTH) levels in patients with Bartter syndrome and lower serum phosphate levels have anecdotally been reported in patients with Gitelman syndrome. In this cross-sectional study, we assessed PTH and phosphate homeostasis in a large cohort of patients with salt-losing tubulopathies. Methods Clinical and laboratory data of 589 patients with Bartter and Gitelman syndrome were provided by members of the European Rare Kidney Diseases Reference Network (ERKNet) and the European Society for Paediatric Nephrology (ESPN). Results A total of 285 patients with Bartter syndrome and 304 patients with Gitelman syndrome were included for analysis. Patients with Bartter syndrome type I and II had the highest median PTH level (7.5 pmol/L) and 56% had hyperparathyroidism (PTH >7.0 pmol/L). Serum calcium was slightly lower in Bartter syndrome type I and II patients with hyperparathyroidism (2.42 versus 2.49 mmol/L; P = .038) compared to those with normal PTH levels and correlated inversely with PTH (r(s) -0.253; P = .009). Serum phosphate and urinary phosphate excretion did not correlate with PTH. Overall, 22% of patients had low serum phosphate levels (phosphate-standard deviation score < -2), with the highest prevalence in patients with Bartter syndrome type III (32%). Serum phosphate correlated with tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) (r(s) 0.699; P < .001), suggesting renal phosphate wasting. Conclusions Hyperparathyroidism is frequent in patients with Bartter syndrome type I and II. Low serum phosphate is observed in a significant number of patients with Bartter and Gitelman syndrome and appears associated with renal phosphate wasting.

Published
2022

38. Differentiation and CRISPR-Cas9-mediated genetic engineering of human intestinal organoids

Author

Martinez-Silgado, Adriana, Yousef Yengej, Fjodor A, Puschhof, Jens, Geurts, Veerle, Boot, Charelle, Geurts, Maarten H, Rookmaaker, Maarten B, Verhaar, Marianne C, Beumer, Joep, Clevers, Hans, Martinez-Silgado, Adriana, Yousef Yengej, Fjodor A, Puschhof, Jens, Geurts, Veerle, Boot, Charelle, Geurts, Maarten H, Rookmaaker, Maarten B, Verhaar, Marianne C, Beumer, Joep, and Clevers, Hans

Abstract

Intestinal organoids are three-dimensional cultures that resemble key aspects of the epithelium of origin. Here, we describe how to differentiate human small intestinal organoids by combining growth media variations and genetic engineering. We detail the differentiation of human intestinal organoids in the presence and absence of BMP agonists to recapitulate a broader scope of functional cell states found in vivo. Using transient overexpression of the transcription factor Neurogenin-3, we describe the enhancement of differentiation toward rare enteroendocrine cells. For complete details on the use and execution of this protocol, please refer to Beumer et al. (2022).

Published
2022

39. Differentiation and CRISPR-Cas9-mediated genetic engineering of human intestinal organoids

Author

Nefro Vasculaire Geneeskunde, MS Nefrologie, Regenerative Medicine and Stem Cells, Circulatory Health, CMM, Cancer, Hubrecht Institute with UMC, Martinez-Silgado, Adriana, Yousef Yengej, Fjodor A., Puschhof, Jens, Geurts, Veerle, Boot, Charelle, Geurts, Maarten H., Rookmaaker, Maarten B., Verhaar, Marianne C., Beumer, Joep, Clevers, Hans, Nefro Vasculaire Geneeskunde, MS Nefrologie, Regenerative Medicine and Stem Cells, Circulatory Health, CMM, Cancer, Hubrecht Institute with UMC, Martinez-Silgado, Adriana, Yousef Yengej, Fjodor A., Puschhof, Jens, Geurts, Veerle, Boot, Charelle, Geurts, Maarten H., Rookmaaker, Maarten B., Verhaar, Marianne C., Beumer, Joep, and Clevers, Hans

Published
2022

40. Substrate Stiffness Determines the Establishment of Apical-Basal Polarization in Renal Epithelial Cells but Not in Tubuloid-Derived Cells

Author

Nefro Vasculaire Geneeskunde, Circulatory Health, Regenerative Medicine and Stem Cells, MS Nefrologie, Hagelaars, Maria J, Yousef Yengej, Fjodor A, Verhaar, Marianne C, Rookmaaker, Maarten B, Loerakker, Sandra, Bouten, Carlijn V C, Nefro Vasculaire Geneeskunde, Circulatory Health, Regenerative Medicine and Stem Cells, MS Nefrologie, Hagelaars, Maria J, Yousef Yengej, Fjodor A, Verhaar, Marianne C, Rookmaaker, Maarten B, Loerakker, Sandra, and Bouten, Carlijn V C

Published
2022

41. Differentiated kidney tubular cell-derived extracellular vesicles enhance maturation of tubuloids

Author

Nefro Vasculaire Geneeskunde, MS Nefrologie, Circulatory Health, Regenerative Medicine and Stem Cells, Lindoso, Rafael Soares, Yousef Yengej, Fjodor A., Voellmy, Franziska, Altelaar, Maarten, Mancheño Juncosa, Estela, Tsikari, Theano, Ammerlaan, Carola M.E., Van Balkom, Bas W.M., Rookmaaker, Maarten B., Verhaar, Marianne C., Masereeuw, Rosalinde, Nefro Vasculaire Geneeskunde, MS Nefrologie, Circulatory Health, Regenerative Medicine and Stem Cells, Lindoso, Rafael Soares, Yousef Yengej, Fjodor A., Voellmy, Franziska, Altelaar, Maarten, Mancheño Juncosa, Estela, Tsikari, Theano, Ammerlaan, Carola M.E., Van Balkom, Bas W.M., Rookmaaker, Maarten B., Verhaar, Marianne C., and Masereeuw, Rosalinde

Published
2022

42. Regulation of Solute Carriers OCT2 and OAT1/3 in the Kidney: A Phylogenetic, Ontogenetic and Cell Dynamic Perspective

Author

Nefro Vasculaire Geneeskunde, Regenerative Medicine and Stem Cells, MS Nefrologie, Circulatory Health, Pou Casellas, Carla, Jansen, Katja, Rookmaaker, Maarten B, Clevers, Hans, Verhaar, Marianne C, Masereeuw, Rosalinde, Nefro Vasculaire Geneeskunde, Regenerative Medicine and Stem Cells, MS Nefrologie, Circulatory Health, Pou Casellas, Carla, Jansen, Katja, Rookmaaker, Maarten B, Clevers, Hans, Verhaar, Marianne C, and Masereeuw, Rosalinde

Published
2022

43. Genetics-first approach improves diagnostics of ESKD patients <50 years old

Author

Genetica, Cancer, Genetica Sectie Genoomdiagnostiek, Pathologie Pathologen staf, Circulatory Health, Genetica Medische Informatica, Child Health, CMM Groep Cuppen, Regenerative Medicine and Stem Cells, MS Nefrologie, Nefrologie, CDL Patiëntenzorg MI, Infection & Immunity, Genetica Klinische Genetica, Snoek, Rozemarijn, van Jaarsveld, Richard H, Nguyen, Tri Q, Peters, Edith D J, Elferink, Martin G, Ernst, Robert F, Rookmaaker, Maarten B, Lilien, Marc R, Spierings, Eric, Goldschmeding, Roel, Knoers, Nine V A M, van der Zwaag, Bert, van Zuilen, Arjan D, van Eerde, Albertien M, Genetica, Cancer, Genetica Sectie Genoomdiagnostiek, Pathologie Pathologen staf, Circulatory Health, Genetica Medische Informatica, Child Health, CMM Groep Cuppen, Regenerative Medicine and Stem Cells, MS Nefrologie, Nefrologie, CDL Patiëntenzorg MI, Infection & Immunity, Genetica Klinische Genetica, Snoek, Rozemarijn, van Jaarsveld, Richard H, Nguyen, Tri Q, Peters, Edith D J, Elferink, Martin G, Ernst, Robert F, Rookmaaker, Maarten B, Lilien, Marc R, Spierings, Eric, Goldschmeding, Roel, Knoers, Nine V A M, van der Zwaag, Bert, van Zuilen, Arjan D, and van Eerde, Albertien M

Published
2022

49. Differentiated kidney tubular cell-derived extracellular vesicles enhance maturation of tubuloids

Author

Lindoso, Rafael Soares, primary, Yousef Yengej, Fjodor A, additional, Voellmy, Franziska, additional, Altelaar, Maarten, additional, Juncosa, Estela Mancheño, additional, Tsikari, Theano, additional, Ammerlaan, Carola M.E., additional, Van Balkom, Bas W.M., additional, Rookmaaker, Maarten B, additional, Verhaar, Marianne C, additional, and Masereeuw, Rosalinde, additional

Published
2022
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50. Substrate Stiffness Determines the Establishment of Apical-Basal Polarization in Renal Epithelial Cells but Not in Tubuloid-Derived Cells

Author

Hagelaars, Maria J., Yousef Yengej, Fjodor A., Verhaar, Marianne C., Rookmaaker, Maarten B., Loerakker, Sandra, Bouten, Carlijn V. C., Modeling in Mechanobiology, Cell-Matrix Interact. Cardiov. Tissue Reg., Soft Tissue Biomech. & Tissue Eng., ICMS Affiliated, and ICMS Core

Subjects
Histology, SDG 3 - Good Health and Well-being, Biomedical Engineering, Bioengineering, SDG 3 – Goede gezondheid en welzijn, Biotechnology
Abstract

Mechanical guidance of tissue morphogenesis is an emerging method of regenerative medicine that can be employed to steer functional kidney architecture for the purpose of bioartificial kidney design or renal tissue engineering strategies. In kidney morphogenesis, apical-basal polarization of renal epithelial cells is paramount for tubule formation and subsequent tissue functions like excretion and resorption. In kidney epithelium, polarization is initiated by integrin-mediated cell-matrix adhesion at the cell membrane. Cellular mechanobiology research has indicated that this integrin-mediated adhesion is responsive to matrix stiffness, raising the possibility to use matrix stiffness as a handle to steer cell polarization. Herein, we evaluate apical-basal polarization in response to 2D substates of different stiffness (1, 10, 50 kPa and glass) in Madin Darby Canine Kidney cells (MDCKs), a classic canine-derived cell model of epithelial polarization, and in tubuloid-derived cells, established from human primary cells derived from adult kidney tissue. Our results show that sub-physiological (1 kPa) substrate stiffness with low integrin-based adhesion induces polarization in MDCKs, while MDCKs on supraphysiological (>10 kPa) stiffness remain unpolarized. Inhibition of integrin, indeed, allows for polarization on the supraphysiological substrates, suggesting that increased cellular adhesion on stiff substrates opposes polarization. In contrast, tubuloid-derived cells do not establish apical-basal polarization on 2D substrates, irrespective of substrate stiffness, despite their ability to polarize in 3D environments. Further analysis implies that the 2D cultured tubuloid-derived cells have a diminished mechanosensitive capacity when presented with different substrate stiffnesses due to immature focal adhesions and the absence of a connection between focal adhesions and the cytoskeleton. Overall, this study demonstrates that apical-basal polarization is a complex process, where cell type, the extracellular environment, and both the mechanical and chemical aspects in cell-matrix interactions performed by integrins play a role.

Published
2021

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