title: Tissue engineering of rat bladder using marrow-derived mesenchymal stem cells and bladder acellular matrix.
abstract: Bladder replacement or augmentation is required in congenital malformations or following trauma or cancer. The current surgical solution involves enterocystoplasty but is associated with high complication rates. Strategies for bladder tissue engineering are thus actively sought to address this unmet clinical need. Because of the poor efficacy of synthetic polymers, the use of bladder acellular matrix (BAM) has been proposed. Indeed when cellular components are removed from xenogenic or allogeneic bladders, the extracellular matrix scaffold thus obtained can be used alone or in combination with stem cells. In this study, we propose the use of BAM seeded with marrow-derived mesenchymal stem cells (MSCs) for bladder tissue engineering. We optimized a protocol for decellularization of bladder tissue from different species including rat, rabbit and swine. We demonstrate the use of non-ionic detergents followed by nuclease digestion results in efficient decellularization while preserving the extracellular matrix. When MSCs were seeded on acellular matrix scaffold, they remained viable and proliferative while adopting a cellular phenotype consistent with their microenvironment. Upon transplantation in rats after partial cystectomy, MSC-seeded BAM proved superior to unseeded BAM with animals recovering nearly 100% normal bladder capacity for up to six months. Histological analyses also demonstrated increased muscle regeneration.
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Coutu
authors.affiliation: Department of Urology, Jewish General Hospital, McGill University, Montreal, Canada; Department of Urology, Alexandria University, Alexandria, Egypt.
authors.forename: Wally
authors.initials: W
authors.lastname: Mahfouz
authors.affiliation: Department of Urology, Jewish General Hospital, McGill University, Montreal, Canada.
authors.forename: Oleg
authors.initials: O
authors.lastname: Loutochin
authors.affiliation: Department of Hematology and Medical Oncology, Pediatrics & Medicine, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Jacques
authors.initials: J
authors.lastname: Galipeau
authors.affiliation: Department of Urology, Jewish General Hospital, McGill University, Montreal, Canada.
authors.forename: Jacques
authors.initials: J
authors.lastname: Corcos
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D011817:Rabbits; D051381:Rats; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D001743:Urinary Bladder / Q000166:cytology*