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De novo reconstitution of a functional mammalian urinary bladder by tissue engineering

Abstract

Human organ replacement is limited by a donor shortage, problems with tissue compatibility, and rejection. Creation of an organ with autologous tissue would be advantageous. In this study, transplantable urinary bladder neo–organs were reproducibly created in vitro from urothelial and smooth muscle cells grown in culture from canine native bladder biopsies and seeded onto preformed bladder–shaped polymers. The native bladders were subsequently excised from canine donors and replaced with the tissue–engineered neo–organs. In functional evaluations for up to 11 months, the bladder neo–organs demonstrated a normal capacity to retain urine, normal elastic properties, and histologic architecture. This study demonstrates, for the first time, that successful reconstitution of an autonomous hollow organ is possible using tissue–engineering methods.

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Figure 1: Surgical technique for cystectomy and preparation of implants.
Figure 2: Performance of bladder implants.
Figure 3: Radiographic cystograms 11 months after subtotal cystectomy.
Figure 4: Gross aspects of subtotal cystectomy control (A and B), polymer–only implant (C and D), and tissue–engineered neo–organ (E and F) retrieved after 11 months.
Figure 5: Histological and immunochemical analysis of implants 6 months after surgery.

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Acknowledgements

This work was supported, in part, by the National Institutes of Health grant RO1 DK 49484, American Medical Systems (Minnetonka, MN), and the German Research Community educational grant Ob 119/1–1. The authors wish to thank Alan B. Retik, Lothar Hertle, and Stephan Roth for their support and Richard Kershen and Kathryn Mehegan for their technical assistance.

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Correspondence to Anthony Atala.

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Oberpenning, F., Meng, J., Yoo, J. et al. De novo reconstitution of a functional mammalian urinary bladder by tissue engineering. Nat Biotechnol 17, 149–155 (1999). https://doi.org/10.1038/6146

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