The peritoneal cavity as a bioreactor for tissue engineering visceral organs: bladder, uterus and vas deferens

Abstract

Our objective was to produce avascular, myofibroblast-rich tissue capsules for use as autologous grafts for hollow, smooth muscle-walled visceral organs-bladder, uterus and vas deferens. To produce tissue for grafting, templates of the appropriate shape were implanted in the peritoneal cavities of rats or rabbits. After 2-3 weeks, the templates were removed, the encapsulating myofibroblast-rich tissue harvested and grafted to replace resected segments of bladder, vas deferens or uterus of the same animals in which the tissue was grown. Bladder grafts showed 100% patency after 14 months and had developed a morphology similar to normal bladder. Tubes of myofibroblast tissue grafted unilaterally into resected rabbit vasa deferentia developed a morphology resembling native tissue, with sperm in the ejaculate indicative of normal function. At 12 weeks after grafting, uterine graft tissue had increased in thickness and developed the morphology of normal uterus, with endometrium overlying several layers of smooth muscle cells (myometrium-like) which were interspersed with collagen fibrils; grafted uterine horns supported embryos to the late stages of gestation. This study shows that myofibroblast tissue produced in the peritoneal cavity is sufficiently plastic to permit differentiation of cells into bladder, vas deferens or uterine smooth muscle. As a method for producing autologous graft material for repair/replacement of these organs, this approach has many benefits over conventional and current tissue-engineering strategies.

Tubularized Urethral Replacement Using Tissue-Engineered Peritoneum-Like Tissue in a Rabbit Model

“…Up to 6 months after the surgery, no urethral stricture occurred. In previous studies, mesothelial cells have been shown to convert into urothelium when placed in the urinary tract [12,13,17]. We observed a similar phenomenon.…”

Cellular Plasticity of Inflammatory Myeloid Cells in the Peritoneal Foreign Body Response

“…For example, when tubes of this myofibroblast-rich tissue (formed around a tubular molding im-planted into the peritoneal cavity for 2 to 3 weeks) are grafted into an autologous artery to replace excised segments, the tissue develops the characteristics of mature vascular smooth muscle and constituent cells express smooth muscle differentiation markers including smoothelin and the smooth muscle myosin isoform SM-2. 6,7 We present here a thorough cellular characterization of the myeloid cells involved in the inflammatory response to implanted foreign material. Specifically, we show that after the initial recruitment of monocytes and granulocytes, macrophages become the predominant cell within both the peritoneal cavity and the tissue capsule.…”

“…On harvest, the tissue has been used as an autologous graft for replacement/repair of hollow smooth muscle organs including blood vessels, bladder, vas deferens, and uterus. [5][6][7] Over the ensuing 2 to 3 months, the grafted tissue undergoes further cell differentiation and tissue remodeling to assume the morphology and function of the host organ. 8 In addition to providing a sterile location to develop myofibroblast-rich tissue for engineering purposes, the peritoneal cavity is a convenient site to investigate the involvement of myeloid cells in the inflammatory response.…”

Allo- and Xeno-Reassembly of Human and Rat Myometrium from Cells and Scaffolds

“…Attempts to create uterine patches date back to 2008, when Campbell et al 6 placed polyethylene bulbs into the peritoneal cavity and grew ''tissue capsules.'' These tissues were composed of myofibroblasts, which likely originated from host peritoneal fluid.…”