title: Functional Human Podocytes Generated in Organoids from Amniotic Fluid Stem Cells.
abstract: Generating kidney organoids using human stem cells could offer promising prospects for research and therapeutic purposes. However, no cell-based strategy has generated nephrons displaying an intact three-dimensional epithelial filtering barrier. Here, we generated organoids using murine embryonic kidney cells, and documented that these tissues recapitulated the complex three-dimensional filtering structure of glomerular slits in vivo and accomplished selective glomerular filtration and tubular reabsorption. Exploiting this technology, we mixed human amniotic fluid stem cells with mouse embryonic kidney cells to establish three-dimensional chimeric organoids that engrafted in vivo and grew to form vascularized glomeruli and tubular structures. Human cells contributed to the formation of glomerular structures, differentiated into podocytes with slit diaphragms, and internalized exogenously infused BSA, thus attaining in vivo degrees of specialization and function unprecedented for donor stem cells. In conclusion, human amniotic fluid stem cell chimeric organoids may offer new paths for studying renal development and human podocyte disease, and for facilitating drug discovery and translational research.
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy; christodoulos.xinaris@marionegri.it cxinaris@yahoo.com.
authors.forename: Christodoulos
authors.initials: C
authors.lastname: Xinaris
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy;
authors.forename: Valentina
authors.initials: V
authors.lastname: Benedetti
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy;
authors.forename: Rubina
authors.initials: R
authors.lastname: Novelli
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy;
authors.forename: Mauro
authors.initials: M
authors.lastname: Abbate
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy;
authors.forename: Paola
authors.initials: P
authors.lastname: Rizzo
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy;
authors.forename: Sara
authors.initials: S
authors.lastname: Conti
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy;
authors.forename: Susanna
authors.initials: S
authors.lastname: Tomasoni
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy;
authors.forename: Daniela
authors.initials: D
authors.lastname: Corna
authors.affiliation: Stem Cells and Regenerative Medicine Laboratory, Foundation Institute of Pediatric Research Fondazione Città della Speranza, Padua, Italy;
authors.forename: Michela
authors.initials: M
authors.lastname: Pozzobon
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy;
authors.forename: Daniela
authors.initials: D
authors.lastname: Cavallotti
authors.affiliation: The Jikei University School of Medicine, Tokyo, Japan;
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokoo
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy;
authors.forename: Marina
authors.initials: M
authors.lastname: Morigi
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy;
authors.forename: Ariela
authors.initials: A
authors.lastname: Benigni
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy; Unit of Nephrology and Dialysis, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy; and Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D007668:Kidney / Q000166:cytology; D051379:Mice; D009940:Organoids / Q000166:cytology*; D050199:Podocytes; D013234:Stem Cells
keywords: filtration slits; glomerulogenesis; human amniotic fluid stem cells; kidney organoids; kidney regeneration; podocyte