title: Human CD133+Renal Progenitor Cells Induce Erythropoietin Production and Limit Fibrosis After Acute Tubular Injury.
abstract: Persistent alterations of the renal tissue due to maladaptive repair characterize the outcome of acute kidney injury (AKI), despite a clinical recovery. Acute damage may also limit the renal production of erythropoietin, with impairment of the hemopoietic response to ischemia and possible lack of its reno-protective action. We aimed to evaluate the effect of a cell therapy using human CD133+renal progenitor cells on maladaptive repair and fibrosis following AKI in a model of glycerol-induced rhabdomyolysis. In parallel, we evaluated the effect of CD133+cells on erythropoietin production. Administration of CD133+cells promoted the restoration of the renal tissue, limiting the presence of markers of injury and pro-inflammatory molecules. In addition, it promoted angiogenesis and protected against fibrosis up to day 60. No effect of dermal fibroblasts was observed. Treatment with CD133+cells, but not with PBS or fibroblasts, limited anemia and increased erythropoietin levels both in renal tissue and in circulation. Finally, CD133+cells contributed to the local production of erythropoietin, as observed by detection of circulating human erythropoietin. CD133+cells appear therefore an effective source for cell repair, able to restore renal functions, including erythropoietin release, and to limit long term maldifferentiation and fibrosis.
authors.affiliation: Department of Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, Italy.
authors.forename: Shikhar
authors.initials: S
authors.lastname: Aggarwal
authors.affiliation: Department of Medical Sciences, Molecular Biotechnology Center, University of Turin, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Grange
authors.affiliation: Department of Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, Italy.
authors.forename: Corinne
authors.initials: C
authors.lastname: Iampietro
authors.affiliation: Department of Medical Sciences, Molecular Biotechnology Center, University of Turin, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Camussi
authors.affiliation: Department of Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Bussolati
mesh_terms: D000071916:AC133 Antigen; D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D000818:Animals; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000096:biosynthesis*; D005355:Fibrosis; D064593:Heterografts; D006801:Humans; D007684:Kidney Tubules / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D000071916:AC133 Antigen; C554270:EPO protein, human; D004921:Erythropoietin