The greater omentum as a site for pancreatic islet transplantation

The greater omentum is a highly vascularized anatomical structure in the peritoneal cavity. Its main components are connective, adipose and vascular cells, along with specialized immune cells. The omentum functions as a site for fat accumulation, it has adhesive properties to control traumatized and inflamed tissues, and a function in local hemostasis, immune responses, and revascularization. Other functions include the absorption of fluids, the phagocytosis of particulate matter, and foreign body reaction. The omentum is catalyzing significant interest for its potential as a site for pancreatic islet and cell transplantation. Our knowledge about this structure, its functions, and its potential as a site for transplantation is poised to grow in the coming years. AnAtomy And Histology of tHe greAter omentum The greater omentum (or epiplón mayor) is an anatomical structure resembling an apron, hanging in the peritoneal cavity, and usually extending over a large area of the abdomen1 (Figure 1, 2). It arises from the greater curvature of the stomach, it crosses the transverse colon and descends in front of abdominal viscera, covering the intestines. There are two portions: the gastrocolic ligament, from the stomach to the transverse colon, and an area below the colon called apron (Figure 2). The omentum is composed of a frame of trabecular connective tissue, intermingled with arteries, veins, lymphatics, fat tissue, and lymphoid aggregates called “milky spots”. Two monolayers of mesothelium contain all the above cell types and structures, with the exception of milky spots – where the mesothelium is interrupted. The macroscopic presentation of the greater omentum depends on the age of the individual, nutrition, pathological conditions and state of stimulation (such as in foreign body reactions, peritoneal dialysis). The right and left Gastroepiploic arteries provide blood supply to the greater omentum. Both arteries derive from the celiac trunk and pass the greater gastric curvature. They progressively branch out towards the stomach and the omentum, giving terminal vessels for the omentum through the right and left epiploic arteries. The omental margin blood supply is provided by numerous capillaries which may have minute anastomoses2 (Figure 3). Milky spots present peculiar convoluted vascular structures termed omental glomeruli3. These microvascular structures show a characteristic architecture at the lateral branches of the epiploic arteries and their terminal branches. The vascular network is usually densely packed with various cells of the reticular system and fat cells. The outstanding feature is that the vascular walls have many fenestrations. Because of the discontinuous mesothelial lining on the milky spots, the glomerulus-like vascular structures are exposed to the peritoneal cavity4. The normal venous drainage parallels the arteries and empties into the portal system5. The gastroepiploic vein increases in diameter after receiving branches from stomach and omentum and empties into the superior mesenteric vein (83%) or in the first part of the splenic portal vein6. The terminal lymphatics form a web with irregular interconnections and with bulging saccular parts. This forms an unusual pattern shaped like flattened tubes7. Some of the 2 M. Pellicciaro, I. Vella, G. Lanzoni, G. Tisone, C. Ricordi saccular terminals are located within the vascular system of milky spots, hence they also are exposed to the abdominal cavity because of the gaps in the mesothelial lining8. The main cellular components of the greater omentum are adipose and connective (mesenchymal) cells. The extracellular matrix is composed of collagen, elastic and reticular fibers, connected by microfibrils. Blood vessels, lymph vessels, and nerve fibers pass through this mesh. The omentum loose connective tissue is areolar, as it presents fixed cells (fibroblasts, fibrocytes, fat cells, pericytes) and mobile cells (histiocytes, monocytes, plasma cells, lymphocytes, eosinophilic granulocytes, mast cells). Fat cells are the most numerous cellular population, and their mass increases significantly in individuals with high Body Mass Index (Figure 4)1. embryologicAl development The embryonic mesoderm is a cell layer that lines the body cavity (coelom) in amniotes. The mesoderm gives rise to multiple derivatives, including the mesothelium a layer of cells that remains as a lining of the abdominal cavity, pleura, mediastinum, and pericardium. The mesothelium lining Figure 1. Scheme of the main constituents of the omentum (Reprinted from “The Greater Omentum”, 1983, Edited by D. Liebermann-Meffert and H. White – with permission from Springer-Nature). Figure 2. Diagram showing peritoneal reflections and topographical relations of the omentum in the sagittal section in humans (Edited from “The Greater Omentum”, 1983, Edited by D. Liebermann-Meffert and H. White – with permission from Springer-Nature). The greater omentum as a site for pancreatic islet transplantation 3 unique structure of its microcirculatory system. In pathological conditions, the omentum performs functions aimed at preserving body homeostasis12,13. The omentum absorbs particles and has an important role in combating abdominal infections (Morison called it the “abdominal policeman”13). During episodes of peritonitis, the omentum rapidly clears bacteria and foreign material that have penetrated into the peritoneal cavity14. Effector mechanisms are mediated by macrophages, neutrophils and, probably, B-lymphocytes. Macrophages are contained within the milky spots, and from there they can migrate into the peritoneal cavity via the openings in the mesothelial layer15. These macrophages phagocyte particles and bacteria from the peritoneal cavity. Subsequently, neutrophils can be recruited from the circulation, extravasate in the the abdominal cavity is associated with a layer of connective tissue, and these tissues are collectively termed peritoneum. The peritoneum forms a serous membrane covering the organs in the abdominal cavity. A double fold of peritoneum constitutes the mesentery, that attaches the intestines to the wall of the abdomen (interestingly, the mesentery has been recently proposed for reclassification as an organ9). The portion of the dorsal mesentery that attaches to the greater curvature of the stomach is known as the dorsal mesogastrium (Figure 5). This structure subsequently expands, ‘balloons’ and then ‘deflates’, giving rise to an apron-like structure (a double layer of peritoneum) that is known as the greater omentum1. The rotation of the primitive stomach and the folding of the dorsal mesentery containing the spleen and pancreas form a dependent large inferior recess know as the lesser sac10. The greater omentum is thus one of the omenta deriving from the folding of the peritoneum; it is located between the greater sac (peritoneal cavity proper) and the lesser sac (omental bursa) of the abdominal cavity. A fusion of the double layer of peritoneum most likely occurs, giving rise to the adult greater omentum11 (Figure 2). pHysiology, function, And pAtHopHysiology of tHe greAter omentum The physiological function of the omentum is still unclear but it is believed to be connected to the Figure 3. Vasculature of the Greater omentum in a human donor, imaged via angiography with barium gelatine. (Reprinted from “The Greater Omentum”, 1983, Edited by D. Liebermann-Meffert and H. White – with permission from