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      Tissue Engineering of Urinary Bladder and Urethra: Advances from Bench to Patients

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          Abstract

          Urinary tract is subjected to many varieties of pathologies since birth including congenital anomalies, trauma, inflammatory lesions, and malignancy. These diseases necessitate the replacement of involved organs and tissues. Shortage of organ donation, problems of immunosuppression, and complications associated with the use of nonnative tissues have urged clinicians and scientists to investigate new therapies, namely, tissue engineering. Tissue engineering follows principles of cell transplantation, materials science, and engineering. Epithelial and muscle cells can be harvested and used for reconstruction of the engineered grafts. These cells must be delivered in a well-organized and differentiated condition because water-seal epithelium and well-oriented muscle layer are needed for proper function of the substitute tissues. Synthetic or natural scaffolds have been used for engineering lower urinary tract. Harnessing autologous cells to produce their own matrix and form scaffolds is a new strategy for engineering bladder and urethra. This self-assembly technique avoids the biosafety and immunological reactions related to the use of biodegradable scaffolds. Autologous equivalents have already been produced for pigs (bladder) and human (urethra and bladder). The purpose of this paper is to present a review for the existing methods of engineering bladder and urethra and to point toward perspectives for their replacement.

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          Engineering Complex Tissues

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            Urine derived cells are a potential source for urological tissue reconstruction.

            Contemporary approaches to tissue engineering and cell therapy for urinary tract reconstruction require invasive tissue biopsies to obtain autologous cells. However, these procedures are associated with potential complications. We determined whether the cells present in urine have characteristics of normal bladder cells and investigated their potential uses for urological reconstructive procedures. A total of 55 urine samples were collected from 15 healthy individuals and 8 patients with vesicoureteral reflux. Urine derived cells were isolated, expanded and tested for progenitor and differentiated cell specific markers using flow cytometry, immunofluorescence and Western immunoblotting. The chromosomal stability of cultured urine derived cells was determined by karyotype analysis. Clones were successfully established from primary cultures of urine derived cells. Isolated cells showed 3 phenotypes, including fully differentiated, differentiating and progenitor-like cells. Some urine derived cells stained positive for the surface markers c-Kit, SSEA4, CD105, CD73, CD91, CD133 and CD44. Two to 7 cells per 100 ml urine were multipoint progenitors that could expand extensively in culture. Single progenitor cells had the ability to differentiate into the cell lineages expressing urothelial, smooth muscle, endothelial and interstitial cell markers. The expression of lineage markers was characterized by Western blot and immunofluorescence analysis. Urine derived cells also maintained a normal karyotype after serial culture. A subpopulation of cells isolated from urine had progenitor cell features and the potential to differentiate into several bladder cell lineages. Urine derived cells could serve as an alternative cell source for urinary tract tissue engineering and reconstruction.
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              Xenogeneic extracellular matrix as a scaffold for tissue reconstruction.

              Bioscaffolds derived from xenogeneic extracellular matrix (ECM) have been used in numerous tissue engineering applications. The safety and efficacy of such scaffolds when used for the repair and reconstruction of numerous body tissues including musculoskeletal, cardiovascular, urogenital and integumentary structures has been shown in both preclinical animal studies and in human clinical studies. More than 200,000 human patients have been implanted with xenogeneic ECM scaffolds. These ECM scaffolds are typically prepared from porcine organs such as small intestine or urinary bladder, which are subjected to decellularization and terminal sterilization without significant loss of the biologic effects of the ECM. The composition of these bioscaffolds includes the structural and functional proteins that are part of native mammalian extracellular matrix. The three-dimensional organization of these molecules distinguishes ECM scaffolds from synthetic scaffold materials and is associated with constructive tissue remodeling instead of scar tissue. The biologic response to these xenogeneic bioscaffolds, including the immune response, is discussed herein. Copyright 2004 Elsevier B.V.
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                Author and article information

                Journal
                ScientificWorldJournal
                ScientificWorldJournal
                TSWJ
                The Scientific World Journal
                Hindawi Publishing Corporation
                1537-744X
                2013
                24 December 2013
                : 2013
                : 154564
                Affiliations
                1Centre LOEX de l'Université Laval, Génie Tissulaire et Régénératrice, LOEX du Centre de Recherche FRQS du Centre de Recherche de CHU de Québec, Axe Médecine Régénératrice, Aile-R Centre Hospitalier Affilié Universitaire de Québec, 1401 18e rue, Québec, QC, Canada G1J 1Z4
                2Département de Chirurgie, Faculté de Médecine, Université Laval, Québec, QC, Canada G1K 7P4
                Author notes

                Academic Editors: P. De Coppi and S. Wang

                Author information
                http://orcid.org/0000-0001-6606-3168
                http://orcid.org/0000-0001-7243-5220
                http://orcid.org/0000-0003-1736-935X
                Article
                10.1155/2013/154564
                3886608
                24453796
                6d32cb52-c077-4daa-83eb-a8d17b1be2ca
                Copyright © 2013 Hazem Orabi et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 August 2013
                : 29 September 2013
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