Renal primordia activate kidney regenerative events in a rat model of progressive renal disease

Barbara Imberti, Daniela Corna, Paola Rizzo, Christodoulos Xinaris, Mauro Abbate, Lorena Longaretti, Paola Cassis, Valentina Benedetti, Ariela Benigni, Carlamaria Zoja, Giuseppe Remuzzi, Marina Morigi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbere0120235
JournalPLoS One
Volume10
Issue number3
DOIs
Publication statusPublished - Mar 26 2015

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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