title: Renal primordia activate kidney regenerative events in a rat model of progressive renal disease.
abstract: New intervention tools for severely damaged kidneys are in great demand to provide patients with a valid alternative to whole organ replacement. For repairing or replacing injured tissues, emerging approaches focus on using stem and progenitor cells. Embryonic kidneys represent an interesting option because, when transplanted to sites such as the renal capsule of healthy animals, they originate new renal structures. Here, we studied whether metanephroi possess developmental capacity when transplanted under the kidney capsule of MWF male rats, a model of spontaneous nephropathy. We found that six weeks post-transplantation, renal primordia developed glomeruli and tubuli able to filter blood and to produce urine in cyst-like structures. Newly developed metanephroi were able to initiate a regenerative-like process in host renal tissues adjacent to the graft in MWF male rats as indicated by an increase in cell proliferation and vascular density, accompanied by mRNA and protein upregulation of VEGF, FGF2, HGF, IGF-1 and Pax-2. The expression of SMP30 and NCAM was induced in tubular cells. Oxidative stress and apoptosis markedly decreased. Our study shows that embryonic kidneys generate functional nephrons when transplanted into animals with severe renal disease and at the same time activate events at least partly mimicking those observed in kidney tissues during renal regeneration.
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy; Fondazione IRCCS-Policlinico San Matteo, Pavia, Italy.
authors: Barbara
authors: B
authors: Imberti
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.
authors: Daniela
authors: D
authors: Corna
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.
authors: Paola
authors: P
authors: Rizzo
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.
authors: Christodoulos
authors: C
authors: Xinaris
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.
authors: Mauro
authors: M
authors: Abbate
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.
authors: Lorena
authors: L
authors: Longaretti
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Centro Ricerche Trapianti "Chiara Cucchi de Alessandri e Gilberto Crespi", Ranica, Bergamo, Italy.
authors: Paola
authors: P
authors: Cassis
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.
authors: Valentina
authors: V
authors: Benedetti
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.
authors: Ariela
authors: A
authors: Benigni
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.
authors: Carlamaria
authors: C
authors: Zoja
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy; IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Centro Ricerche Trapianti "Chiara Cucchi de Alessandri e Gilberto Crespi", Ranica, Bergamo, Italy; Unit of Nephrology and Dialysis, A.O. Papa Giovanni XXIII, Bergamo, Italy.
authors: Giuseppe
authors: G
authors: Remuzzi
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.
authors: Marina
authors: M
authors: Morigi
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D049109:Cell Proliferation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000637:transplantation; D015870:Gene Expression; D006085:Graft Survival; D007674:Kidney Diseases / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016030:Kidney Transplantation / Q000379:methods; D008297:Male; D018919:Neovascularization, Physiologic; D018384:Oxidative Stress; D051381:Rats; D012038:Regeneration / Q000235:genetics
chemical_list: D015415:Biomarkers