Human Allogeneic Liver-Derived Progenitor Cells Significantly Improve NAFLD Activity Score and Fibrosis in Late-Stage NASH Animal Model.

Accumulated experimental and clinical evidence supports the development of human allogeneic liver-derived progenitor cells (HALPCs) to treat fibro-inflammatory liver diseases. The aim of the present study was to evaluate their therapeutic effect in a non-alcoholic steatohepatitis (NASH)-STAM mouse model. The immune signaling characteristics of HALPCs were first assessed in vitro. Upon inflammation treatment, HALPCs secreted large amounts of potent bioactive prostaglandin E2 and indoleamine 2,3-dioxygenase, which significantly reduced CD4+ T-lymphocyte proliferation and secretion of proinflammatory cytokines. In vivo, HALPCs were intravenously administered as single or triple shots (of a dose of 12.5 × 106 cells/kg BW) in STAM mice. Transplantation of HALPCs was associated with a significant decrease in the NAFLD activity score at an early stage and in both inflammation and hepatocyte ballooning scores in late-stage NASH. Sirius red staining analyses revealed decreased collagen deposition in the pericentral region at both stages of NASH. Altogether, these findings showed the anti-inflammatory and anti-fibrotic features of HALPCs in an in vivo NASH model, which suggests their potential to reverse the progression of this chronic fibro-inflammatory disease.

Endometriosis and infertility.

Endometriosis remains a very enigmatic and perplexing disease. The exact mechanism by which endometriosis causes infertility is still unclear. In the present paper, we will review possible mechanisms leading to subfertility or infertility in women with endometriosis and examine them according to location. Endometriosis in the pelvic cavity is a pathology associated with a general inflammatory response and should therefore be considered an inflammatory disease. Inflammatory changes affect the peritoneal fluid and hence the intratubal milieu, since the ampulla (where fertilization takes place) is exposed to peritoneal fluid through the fimbria. Any inflammatory change at this level may therefore impact fertilization and natural conception. The relationship between ovarian endometriomas and infertility may, of course, be explained by the presence of periovarian endometriosis. In the ovary, fibrosis observed in some cortical areas is induced by the inflammatory reaction caused by the presence of endometriomas. The association between fibrosis and a reduced ovarian reserve was demonstrated. Upregulated recruitment and the subsequent demise of early follicles may result in focal exhaustion of primordial follicles. Burn-out of early follicles by a local pelvic inflammatory environment caused by endometriomas may therefore be suggested. However, intraovarian inflammation, subsequent fibrosis and depletion of the ovarian reserve constitute another reason that should also be given due consideration. In addition, surgery should not be ruled out as a possible cause of ovarian reserve depletion. In conclusion, potential mechanisms leading to infertility are numerous, and while some of them remain hypothetical for now, others are supported by clear evidence. These possible mechanisms were reviewed in the present paper.

Absence of intestinal inflammation and postoperative ileus in a mouse model of laparoscopic surgery.

BACKGROUND: Postoperative ileus (POI) is characterized by impaired gastrointestinal motility resulting from intestinal handling-associated inflammation. The introduction of laparoscopic surgery has dramatically reduced the duration of POI. However, it remains unclear to what extent this results in a reduction of intestinal inflammation. The aim of the present study is to compare the degree of intestinal inflammation and gastrointestinal transit following laparoscopic surgery and open abdominal surgery. METHODS: Mice were subjected to laparoscopic surgery or laparotomy alone or, in combination with standardized intestinal manipulation of the small bowel (IM). Gastrointestinal transit and intestinal inflammation were assessed 24 h after surgery by the number of myeloperoxidase (MPO) positive cells and the level of cytokine expression. The recovery time and the degree of inflammation were also analyzed in patients subjected to colectomy under open conditions (laparotomy) or laparoscopic conditions. KEY RESULTS: Mice undergoing IM by laparotomy (open IM), but not by laparoscopy (Lap IM) developed a significant delay in gastrointestinal transit compared to laparotomy or laparoscopy alone. In addition, there was significant intestinal inflammation only after open IM. Similarly, cytokine levels in peritoneal lavage fluid were lower while recovery time was faster in patients subjected to colectomy under laparoscopic conditions compared to open colectomy. CONCLUSIONS & INFERENCES: Our data confirms that intestinal inflammation is underlying the delayed gastrointestinal transit observed after open surgery. Most importantly, we demonstrate that intestinal inflammation under laparoscopic conditions is significantly lower compared to open surgery, most likely explaining the faster recovery following laparoscopic surgery.