title: In vivo maturation of functional renal organoids formed from embryonic cell suspensions.
abstract: The shortage of transplantable organs provides an impetus to develop tissue-engineered alternatives. Producing tissues similar to immature kidneys from simple suspensions of fully dissociated embryonic renal cells is possible in vitro, but glomeruli do not form in the avascular environment. Here, we constructed renal organoids from single-cell suspensions derived from E11.5 kidneys and then implanted these organoids below the kidney capsule of a living rat host. This implantation resulted in further maturation of kidney tissue, formation of vascularized glomeruli with fully differentiated capillary walls, including the slit diaphragm, and appearance of erythropoietin-producing cells. The implanted tissue exhibited physiologic functions, including tubular reabsorption of macromolecules, that gained access to the tubular lumen on glomerular filtration. The ability to generate vascularized nephrons from single-cell suspensions marks a significant step to the long-term goal of replacing renal function by a tissue-engineered kidney.
authors.affiliation: Department of Molecular Medicine, Mario Negri Institute for Pharmacological Research, Bergamo, Italy. christodoulos.xinaris@marionegri.it
authors.forename: Christodoulos
authors.initials: C
authors.lastname: Xinaris
authors.forename: Valentina
authors.initials: V
authors.lastname: Benedetti
authors.forename: Paola
authors.initials: P
authors.lastname: Rizzo
authors.forename: Mauro
authors.initials: M
authors.lastname: Abbate
authors.forename: Daniela
authors.initials: D
authors.lastname: Corna
authors.forename: Nadia
authors.initials: N
authors.lastname: Azzollini
authors.forename: Sara
authors.initials: S
authors.lastname: Conti
authors.forename: Mathieu
authors.initials: M
authors.lastname: Unbekandt
authors.forename: Jamie A
authors.initials: JA
authors.lastname: Davies
authors.forename: Marina
authors.initials: M
authors.lastname: Morigi
authors.forename: Ariela
authors.initials: A
authors.lastname: Benigni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D000818:Animals; D021522:Bioartificial Organs; D007668:Kidney / Q000098:blood supply / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D016030:Kidney Transplantation / Q000379:methods; D008297:Male; D051379:Mice; D009940:Organoids / Q000166:cytology / Q000196:embryology* / Q000637:transplantation; D051381:Rats; D011923:Rats, Nude; D023822:Tissue Engineering / Q000379:methods*; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage
chemical_list: D042461:Vascular Endothelial Growth Factor A