Understanding bladder regeneration: Smooth muscle ontogeny

Purpose: We determined the origin of smooth muscle cells in acellular bladd er matrix grafts. Materials and Methods: A total of 15 female Sprague-Dawley rats underwent p artial cystectomy and grafting with an acellular matrix derived from rat bl adder. The grafts were examined 1, 2, 3 and 4 weeks after grafting by immun ohistochemical studies for smooth muscle markers and by transmission electr on microscopy for smooth muscle morphology. Bladder matrix and bladder epit helium recombinants were created and grafted subcutaneously and under the r enal capsule in nude mice. Recombinants were examined 1, 2, 3 and 4 weeks p ostoperatively by immunohistochemical studies for bladder epithelium and bl adder smooth muscle. Results: Smooth muscle ingrowth into acellular matrix was initially seen at 2 weeks. The immunohistochemical and electron microscopic characteristics of the cells were similar to those of fetal smooth muscle 2 weeks and newbo rn smooth muscle 4 weeks after grafting. Matrix epithelium recombinants dis played mature bladder epithelium with 3 to 7 layers but they did not suppor t the ingrowth of smooth muscle cells. Conclusions: Mature bladder smooth muscle cells undergo dedifferentiation, migration and redifferentiation to repopulate an acellular matrix graft. It is unlikely that adult fibroblasts from the surrounding tissue are induced by epithelium and matrix to form smooth muscle. The contractile behavior o f bladder substitute materials likely reflects the properties of the host b ladder.