title: Renal cells from spermatogonial germline stem cells protect against kidney injury.
abstract: Spermatogonial stem cells reside in specific niches within seminiferous tubules and continuously generate differentiating daughter cells for production of spermatozoa. Although spermatogonial stem cells are unipotent, these cells are able to spontaneously convert to germline cell-derived pluripotent stem cells (GPSCs) in vitro. GPSCs have many properties of embryonic stem cells and are highly plastic, but their therapeutic potential in tissue regeneration has not been fully explored. Using a novel renal epithelial differentiation protocol, we obtained GPSC-derived tubular-like cells (GTCs) that were functional in vitro, as demonstrated through transepithelial electrical resistance analysis. In mice, GTCs injected after ischemic renal injury homed to the renal parenchyma, and GTC-treated mice showed reduced renal oxidative stress, tubular apoptosis, and cortical damage and upregulated tubular expression of the antioxidant enzyme hemeoxygenase-1. Six weeks after ischemic injury, kidneys of GTC-treated mice had less fibrosis and inflammatory infiltrate than kidneys of vehicle-treated mice. In conclusion, we show that GPSCs can be differentiated into functionally active renal tubular-like cells that therapeutically prevent chronic ischemic damage in vivo, introducing the potential utility of GPSCs in regenerative cell therapy.
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, and.
authors.forename: Letizia
authors.initials: L
authors.lastname: De Chiara
authors.forename: Sharmila
authors.initials: S
authors.lastname: Fagoonee
authors.forename: Andrea
authors.initials: A
authors.lastname: Ranghino
authors.forename: Stefania
authors.initials: S
authors.lastname: Bruno
authors.forename: Giovanni
authors.initials: G
authors.lastname: Camussi
authors.forename: Emanuela
authors.initials: E
authors.lastname: Tolosano
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Silengo
authors.forename: Fiorella
authors.initials: F
authors.lastname: Altruda
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology / Q000517:prevention & control / Q000601:surgery*; D053687:Adult Stem Cells / Q000637:transplantation*; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000494:pharmacology; D017097:Electric Impedance; D058732:Embryoid Bodies; D005260:Female; D005355:Fibrosis; D020869:Gene Expression Profiling; D051547:Heme Oxygenase-1 / Q000032:analysis; D007676:Kidney Failure, Chronic / Q000517:prevention & control; D007684:Kidney Tubules / Q000166:cytology*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D018384:Oxidative Stress; D011183:Postoperative Complications / Q000209:etiology; D044968:Regenerative Medicine / Q000379:methods; D015427:Reperfusion Injury / Q000473:pathology / Q000601:surgery*; D012671:Seminiferous Tubules / Q000166:cytology; D013093:Spermatogonia / Q000166:cytology*; D033581:Stem Cell Transplantation / Q000009:adverse effects; D013724:Teratoma / Q000209:etiology
chemical_list: D015415:Biomarkers; D024141:Collagen Type IV; D008565:Membrane Proteins; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse