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UNDERSTANDING BLADDER REGENERATION: SMOOTH MUSCLE ONTOGENY
UNDERSTANDING BLADDER REGENERATION tion with bladder matrix and bladder epithelium. Since immature smooth muscle cells and myofibroblasts are similar at 1 point yet eventually different, future efforts to direct these cells toward more normal development would have important implications not only in patients with abnormal bladders, but also i n those with abnormal wound healing or proliferative disease. CONCLUSIONS
Mature bladder smooth muscle cells undergo dedifferentiation, migration a n d redifferentiation to repopulate an acellular matrix graft. It is unlikely that adult fibroblasts from the surrounding tissue a r e induced by epithelium and matrix to form smooth muscle. The contractile behavior of bladder substitute materials likely reflects t h e properties of the host bladder.
Dr. Joseph Goodman performed t h e electron microscopic analysis of native and grafted bladder tissue, and anticytokeratin antibodies to cytokeratins 7, 8 a n d 14 were provided by Dr. E. B. Lane, University of Dundee. REFERENCES
1. McDougal, W. S.: Metabolic complications of urinary intestinal diversion. J. Urol., 141: 1199, 1992. 2. Sutherland, R. S., Baskin, L. S., Hayward, S. W. and Cunha,
3. 4.
5.
G. R.: Regeneration of bladder urothelium, smooth muscle, blood vessels and nerves into an acellular tissue matrix. J. Urol., 156: 571, 1996. Probst, M., Dahiya, R., Carrier, S. and Tanagho, E. A,: Reproduction of functional smooth muscle tissue and partial bladder replacement. Brit. J. Urol., 7 9 505, 1997. Kropp, B. P., Rippy, M. K., Badylak, S. F., Adams, M. C., Keating, M. A,, Rink, R. C. and Thor, K. B.: Regenerative urinary bladder augmentation using small intestinal submucosa: urodynamic and histopathologicassessment in long-term canine bladder augmentations. J . Urol., 155: 2098, 1996. Pope, J . C. T., Davis, M. M., Smith, E. R., Jr., Walsh, M. J., Ellison, P. K., Rink, R. C. and Kropp, B. P.: The ontogeny of canine small intestinal submucosa regenerated bladder. J. Urol., 158 1105, 1997. Vaught, J. D., %ODD, B. P.. Sawyer. B. D., RiDDY, M. K., Badylak, S. F., Shannon, H. E. &.d Thor, K. B1:-Detrusor regeneration in the rat using porcine small intestinal submu-
-
6.
1105
cosal grafts: functional innervation and receptor expression. J. Urol., 155 374, 1996. 7. Kropp, B. P., Sawyer, B. D., Shannon, H. E., Rippy, M. K., Badylak, S. F., Adams, M. C., Keating, M. A,, Rink, R. C. and Thor, K. B.: Characterization of small intestinal submucosa regenerated canine detrusor: assessment of reinnervation, in vitro compliance and contractility. J. Urol., 156 599, 1996. 8. Schurch, W., Seemayer, T. and Gabbiani, G.: Myofibroblast. In: Histology for Pathologists. Edited by S. Sternberg. New York Raven Press, chapt. 109, 1992. 9. Baskin, L. S., Hayward, S. W., Young, P. F. and Cunha, G. R.: Ontogeny of the rat bladder: smooth muscle and epithelial differentiation. Acta Anat., 1 5 5 163, 1996. 10. Wu, H. Y., Baskin, L. S., Blakey, C., Goodman, J . and Cunha, G. R.: Ultrastructural smooth muscle ontogeny of the rat bladder. In: Advances in Bladder Research. Edited by L. S. Baskin and S. W. Hayward. New York: Plenum, 1999. 11. DiSandro, M. J., Li, Y., Baskin, L. S., Hayward, S. and Cunha, G.: Mesenchymal-epithelial interactions in bladder smooth muscle development: epithelial specificity. J . Urol., 160:1040, 1998. 12. Darby, I., Skalli, 0. and Gabbiani, G.: Alpha-smooth muscle
actin is transiently expressed by myofibroblasts during experimental wound healing. Lab. Invest., 63: 21, 1990. 13. Buoro, S., Ferrarese, P., Chiavegato, A., Roelofs, M., Scatena, M., Pauletto, P., Passerini-Glazel, G., Pagano, F. and Sartore, S.: Myofibroblast-derived smooth muscle cells during remodelling of rabbit urinary bladder wall induced by partial outflow obstruction. Lab. Invest., 69: 589, 1993. 14. Sappino, A. P., Schurch, W. and Gabbiani, G.: Differentiation repertoire of fibroblastic cells: expression of cytoskeletal proteins as marker of phenotypic modulations. Lab. Invest., 63: 144, 1990. 15. Taderera, J.: Control of lung differentiation in vitro. Dev. Biol., 1 6 489, 1967. 16. Haffen, K., Kedinger, M. and Simon-Assmann,P.: Mesenchymedependent differentiation of epithelial progenitor cells in the gut. J. Ped. Gastroenterol. Nutr., 6 14, 1987. 17. Baskin, L. S., Hayward, S. W., Young, P. and Cunha, G. R.: Role
of mesenchymal-epithelial interactions in normal bladder development. J . Urol., 156 1820, 1996. 18. Hayward, S. W., Del Buono, R., Deshpande, N. and Hall, P. A.: A functional model of adult human prostate epithelium. The role of androgens and stroma in architectural organisation and the maintenance of differentiated secretory function. J. Cell Sci., 1 0 2 361, 1992.
DISCUSSION
Dr. Anthony A. Atala. Have you analyzed growth factor biology in these matrices? Dr. Hsi-Yang Wu. No, we have not analyzed the matrix for growth factors.
Mature bladder smooth muscle cells undergo dedifferentiation, migration a n d redifferentiation to repopulate an acellular matrix graft. It is unlikely that adult fibroblasts from the surrounding tissue a r e induced by epithelium and matrix to form smooth muscle. The contractile behavior of bladder substitute materials likely reflects t h e properties of the host bladder.
Dr. Joseph Goodman performed t h e electron microscopic analysis of native and grafted bladder tissue, and anticytokeratin antibodies to cytokeratins 7, 8 a n d 14 were provided by Dr. E. B. Lane, University of Dundee. REFERENCES
1. McDougal, W. S.: Metabolic complications of urinary intestinal diversion. J. Urol., 141: 1199, 1992. 2. Sutherland, R. S., Baskin, L. S., Hayward, S. W. and Cunha,
3. 4.
5.
G. R.: Regeneration of bladder urothelium, smooth muscle, blood vessels and nerves into an acellular tissue matrix. J. Urol., 156: 571, 1996. Probst, M., Dahiya, R., Carrier, S. and Tanagho, E. A,: Reproduction of functional smooth muscle tissue and partial bladder replacement. Brit. J. Urol., 7 9 505, 1997. Kropp, B. P., Rippy, M. K., Badylak, S. F., Adams, M. C., Keating, M. A,, Rink, R. C. and Thor, K. B.: Regenerative urinary bladder augmentation using small intestinal submucosa: urodynamic and histopathologicassessment in long-term canine bladder augmentations. J . Urol., 155: 2098, 1996. Pope, J . C. T., Davis, M. M., Smith, E. R., Jr., Walsh, M. J., Ellison, P. K., Rink, R. C. and Kropp, B. P.: The ontogeny of canine small intestinal submucosa regenerated bladder. J. Urol., 158 1105, 1997. Vaught, J. D., %ODD, B. P.. Sawyer. B. D., RiDDY, M. K., Badylak, S. F., Shannon, H. E. &.d Thor, K. B1:-Detrusor regeneration in the rat using porcine small intestinal submu-
-
6.
1105
cosal grafts: functional innervation and receptor expression. J. Urol., 155 374, 1996. 7. Kropp, B. P., Sawyer, B. D., Shannon, H. E., Rippy, M. K., Badylak, S. F., Adams, M. C., Keating, M. A,, Rink, R. C. and Thor, K. B.: Characterization of small intestinal submucosa regenerated canine detrusor: assessment of reinnervation, in vitro compliance and contractility. J. Urol., 156 599, 1996. 8. Schurch, W., Seemayer, T. and Gabbiani, G.: Myofibroblast. In: Histology for Pathologists. Edited by S. Sternberg. New York Raven Press, chapt. 109, 1992. 9. Baskin, L. S., Hayward, S. W., Young, P. F. and Cunha, G. R.: Ontogeny of the rat bladder: smooth muscle and epithelial differentiation. Acta Anat., 1 5 5 163, 1996. 10. Wu, H. Y., Baskin, L. S., Blakey, C., Goodman, J . and Cunha, G. R.: Ultrastructural smooth muscle ontogeny of the rat bladder. In: Advances in Bladder Research. Edited by L. S. Baskin and S. W. Hayward. New York: Plenum, 1999. 11. DiSandro, M. J., Li, Y., Baskin, L. S., Hayward, S. and Cunha, G.: Mesenchymal-epithelial interactions in bladder smooth muscle development: epithelial specificity. J . Urol., 160:1040, 1998. 12. Darby, I., Skalli, 0. and Gabbiani, G.: Alpha-smooth muscle
actin is transiently expressed by myofibroblasts during experimental wound healing. Lab. Invest., 63: 21, 1990. 13. Buoro, S., Ferrarese, P., Chiavegato, A., Roelofs, M., Scatena, M., Pauletto, P., Passerini-Glazel, G., Pagano, F. and Sartore, S.: Myofibroblast-derived smooth muscle cells during remodelling of rabbit urinary bladder wall induced by partial outflow obstruction. Lab. Invest., 69: 589, 1993. 14. Sappino, A. P., Schurch, W. and Gabbiani, G.: Differentiation repertoire of fibroblastic cells: expression of cytoskeletal proteins as marker of phenotypic modulations. Lab. Invest., 63: 144, 1990. 15. Taderera, J.: Control of lung differentiation in vitro. Dev. Biol., 1 6 489, 1967. 16. Haffen, K., Kedinger, M. and Simon-Assmann,P.: Mesenchymedependent differentiation of epithelial progenitor cells in the gut. J. Ped. Gastroenterol. Nutr., 6 14, 1987. 17. Baskin, L. S., Hayward, S. W., Young, P. and Cunha, G. R.: Role
of mesenchymal-epithelial interactions in normal bladder development. J . Urol., 156 1820, 1996. 18. Hayward, S. W., Del Buono, R., Deshpande, N. and Hall, P. A.: A functional model of adult human prostate epithelium. The role of androgens and stroma in architectural organisation and the maintenance of differentiated secretory function. J. Cell Sci., 1 0 2 361, 1992.
DISCUSSION
Dr. Anthony A. Atala. Have you analyzed growth factor biology in these matrices? Dr. Hsi-Yang Wu. No, we have not analyzed the matrix for growth factors.