Cellular exchange in an endometriosis-adhesion model using GFP transgenic mice.

BACKGROUND: Endometriosis is a debilitating disease that affects women of reproductive age and may lead to impaired fertility. Cell attachment, invasion of the underlying tissue, and vascular ingrowth are important processes in endometrial lesion development. However, the degree of cellular exchange between host peritoneum and endometrial tissue is unclear. METHODS: An experimental endometriosis model was employed whereby uterine horn fragments from wild-type mice were implanted into genetically identical eGFP (enhanced green fluorescent protein) host mice and vice versa. Hormone sensitivity of the ectopic lesions was assessed and cellular exchange determined histologically. RESULTS: White cyst-like lesions developed from implanted fibrin-rich fragments by day 7. Lesions consisted of a well-developed stroma with glandular and luminal epithelium. Both ovariectomy and treatment with a GnRH agonist, leuprorelin, resulted in the suppression of ectopic lesion growth, whereas estradiol treatment increased the size of the ectopic lesion (4 mice per group on day 14). Ingrowth and outgrowth of blood vessels was apparent as well as the exchange of cells between host peritoneum and lesion. CONCLUSION: These findings support the proposal that there is a close cellular interplay between host peritoneum and ectopic tissue and the suitability of this mouse model to study these interactions.

Remodelling of adipose tissue during experimental omental adhesion formation.

BACKGROUND: Peritoneal adhesions are fibrous bands of tissue connecting normally separated organs and frequently involve the fat-laden greater omentum. Remodelling of fibrin-rich exudate under reduced fibrinolytic conditions is thought to initiate adhesion formation following surgery. It is unclear whether adhesions that involve the omentum develop in a similar manner. To improve understanding of omental adhesion formation, adipose tissue distribution, cell proliferation and procollagen type I gene expression were investigated in a murine surgical model and in established omental adhesions from patients undergoing abdominal surgery. METHODS: Experimental murine omental adhesions and human omental adhesions were analysed for signs of tissue remodelling using histology, immunohistochemistry and in situ hybridization. RESULTS: Murine omental tissue showed intense inflammation and reduced adipose tissue 3-7 days after surgery, but increased cellularity and collagen production. Adipose tissue remodelling was reversible with increased adipose tissue and decreased cell proliferation and procollagen type I gene expression, shown by proliferating cell nuclear antigen immunolocalization and in situ hybridization respectively. Human omental adhesions were heterogeneous, with varying amounts of fibrotic and adipose-rich regions, although most displayed proliferating and collagen-producing cells. CONCLUSION: Omental adhesions are not static scar tissue as traditionally thought, but undergo active adipose tissue remodelling over-time.

Structure and function of mesothelial cells.

The mesothelium was first described about 180 years ago but only in the last twenty years have we begun to appreciate the roles that mesothelial cells play in maintaining normal serosal membrane integrity and function. Mesothelial cells are sentinel cells that can sense and respond to signals within their microenvironment. They secrete glycosaminoglycans and surfactant to allow the parietal and visceral serosa to slide over each other. They actively transport fluids, cells and particulates across the serosal membrane and between serosal cavities. They synthesise and secrete a diverse array of mediators in response to external signals which play important roles in regulating inflammatory, immune and tissue repair responses. In addition, they are likely to protect from peritoneal dissemination of tumours until the integrity of the mesothelium is breached. Although the importance of the mesothelial cell is being realised, we still do not understand the mechanisms regulating many of their functions. How the cells communicate with each other and surrounding cells, whether mesothelial cells differentiate into different cell types or if a mesothelial stem cell exists, the mechanisms regulating mesothelial repair and the role mesothelial cells play in serosal pathologies, all need further study. Although it has long been accepted that mesothelial cells are similar irrespective of site or species, apart from morphology, few studies have truly compared biochemical and functional characteristics of these cells between species and within different anatomical sites. In a recent study examining the effect of aging on human peritoneal mesothelial cells, there was a positive correlation between the age of the donor's cells and the proinflammatory profile. Although mesothelial cells share many similarities, it is likely that functional and physiological adaptation will alter these cells. Addressing these questions are paramount if we hope to find better ways to protect serosal integrity and prevent peritoneal dissemination of tumours.