title: Clonal, self-renewing and differentiating human and porcine urothelial cells, a novel stem cell population.
abstract: Although urothelial progenitor-like cells have been described in the human urinary tract, the existence of stem cells remains to be proven. Using a culture system that favors clonogenic epithelial cell growth, we evaluated and characterized clonal human urothelial cells. We isolated human urothelial cells that were clonogenic, capable of self-renewal and could develop into fully differentiated urothelium once re-implanted into the subcapsular space of nude mice. In addition to final urothelial cell differentiation, spontaneous formation of bladder-like microstructures was observed. By examining an epithelial stem cell signature marker, we found p63 to correlate with the self-renewal capacity of the isolated human urothelial clonal populations. Since a clinically relevant, long-term model for functional reconstitution of human cells does not exist, we sought to establish a culture method for porcine urothelial cells in a clinically relevant porcine model. We isolated cells from porcine ureter, urethra and bladder that were clonogenic and capable of self-renewal and differentiation into fully mature urothelium. In conclusion, we could isolate human and porcine cell populations, behaving as urothelial stem cells and showing clonogenicity, self-renewal and, once re-implanted, morphological differentiation.
authors.affiliation: Laboratory for Regenerative Medicine and Pharmacobiology, Institute for Bioengineering, School of Life Sciences and School of Engineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Hans M
authors.initials: HM
authors.lastname: Larsson
authors.affiliation: Laboratory of Experimental Surgery, Department of Experimental Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland ; Laboratory of Stem Cell Dynamics, Institute for Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Francois
authors.initials: F
authors.lastname: Gorostidi
authors.affiliation: Laboratory for Regenerative Medicine and Pharmacobiology, Institute for Bioengineering, School of Life Sciences and School of Engineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hubbell
authors.affiliation: Laboratory of Experimental Surgery, Department of Experimental Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland ; Laboratory of Stem Cell Dynamics, Institute for Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Yann
authors.initials: Y
authors.lastname: Barrandon
authors.affiliation: Laboratory for Regenerative Medicine and Pharmacobiology, Institute for Bioengineering, School of Life Sciences and School of Engineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland ; Laboratory of Experimental Pediatric Urology, Department of Pediatric Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Frey
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002469:Cell Separation; D002999:Clone Cells / Q000166:cytology; D006801:Humans; D051379:Mice; D013234:Stem Cells / Q000166:cytology*; D013552:Swine; D014513:Ureter / Q000166:cytology; D019459:Urothelium / Q000166:cytology*