title: Cystogenic potential of CD133+ progenitor cells of human polycystic kidneys.
abstract: In autosomal dominant polycystic kidney disease, cysts arise focally and disrupt normal renal tissue leading to renal failure. In the present study, we show that cyst-lining cells express the stem cell marker CD133. CD133+ progenitor cells isolated from polycystic kidney, carrying mutations of PKD genes, showed a dedifferentiated phenotype similar to CD133+ progenitor cells from normal kidney. However, these cells were more proliferative and presented a defective epithelial differentiation phenotype with respect to normal renal CD133+ cells as they were not able to express all tubular epithelial cell markers when cultured in epithelial differentiation medium. Polycystic CD133+ cells, in contrast to normal renal CD133+ cells, formed cysts in vitro in a three-dimensional culture system and in vivo when injected subcutaneously within Matrigel in SCID mice. Rapamycin treatment reduced in vitro proliferation of polycystic CD133+ cells and decreased cystogenesis both in vitro and in vivo. The in vitro epithelial differentiation was only partially improved by rapamycin. These results indicate that polycystic CD133+ cells retain a dedifferentiated phenotype and the ability to generate cysts.
authors.affiliation: Department of Internal Medicine, Research Center for Experimental Medicine (CeRMS) and Center for Molecular Biotechnology, San Giovanni Battista Hospital, University of Torino, Torino, Italy.
authors.forename: Raquel
authors.initials: R
authors.lastname: Carvalhosa
authors.forename: Ilaria
authors.initials: I
authors.lastname: Deambrosis
authors.forename: Paola
authors.initials: P
authors.lastname: Carrera
authors.forename: Chiara
authors.initials: C
authors.lastname: Pasquino
authors.forename: Francesca
authors.initials: F
authors.lastname: Rigo
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ferrari
authors.forename: Fedele
authors.initials: F
authors.lastname: Lasaponara
authors.forename: Andrea
authors.initials: A
authors.lastname: Ranghino
authors.forename: Luigi
authors.initials: L
authors.lastname: Biancone
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Segoloni
authors.forename: Benedetta
authors.initials: B
authors.lastname: Bussolati
authors.forename: Giovanni
authors.initials: G
authors.lastname: Camussi
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D020125:Mutation, Missense; D010455:Peptides / Q000378:metabolism*; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology; D013234:Stem Cells / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D050396:TRPP Cation Channels / Q000235:genetics; D014183:Transplantation, Heterologous
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D010455:Peptides; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D050396:TRPP Cation Channels; C000606023:PROM1 protein, human; C000606024:Prom1 protein, mouse; C546842:MTOR protein, human