CellR4 2017; 5 (3): e2410 The greater omentum as a site for pancreatic islet transplantation M. Pellicciaro1, I. Vella1, G. Lanzoni2, G. Tisone1, C. Ricordi2 1Liver Transplant Center, Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy. 2Diabetes Research Institute and Cell Transplant Center, University of Miami, Miami, FL, USA. Corresponding Author: Marco Pellicciaro, MD student; e-mail: [email protected] Keywords: Omentum, Greater omentum, Islet of Lang- fat tissue, and lymphoid aggregates called “milky erhans, Islet of Langerhans transplantation, T1D, Islet trans- spots”. Two monolayers of mesothelium contain plantation, Pancreatic islet transplantation, Diabetes type 1, all the above cell types and structures, with the Beta cell transplantation. exception of milky spots – where the mesotheli- um is interrupted. The macroscopic presentation ABSTRACT of the greater omentum depends on the age of The greater omentum is a highly vascularized the individual, nutrition, pathological conditions anatomical structure in the peritoneal cavity. Its and state of stimulation (such as in foreign body main components are connective, adipose and reactions, peritoneal dialysis). The right and left vascular cells, along with specialized immune Gastroepiploic arteries provide blood supply to cells. The omentum functions as a site for fat ac- the greater omentum. Both arteries derive from cumulation, it has adhesive properties to control the celiac trunk and pass the greater gastric cur- traumatized and inflamed tissues, and a function vature. They progressively branch out towards in local hemostasis, immune responses, and re- the stomach and the omentum, giving terminal vascularization. Other functions include the ab- vessels for the omentum through the right and left sorption of fluids, the phagocytosis of particulate epiploic arteries. The omental margin blood supply matter, and foreign body reaction. The omentum is provided by numerous capillaries which may is catalyzing significant interest for its potential have minute anastomoses2 (Figure 3). Milky spots as a site for pancreatic islet and cell transplan- present peculiar convoluted vascular structures tation. Our knowledge about this structure, its termed omental glomeruli3. These microvascular functions, and its potential as a site for transplan- structures show a characteristic architecture at the tation is poised to grow in the coming years. lateral branches of the epiploic arteries and their terminal branches. The vascular network is usually densely packed with various cells of the reticular ANATOMY AND HISTOLOGY system and fat cells. The outstanding feature is OF THE GREATER OMENTUM that the vascular walls have many fenestrations. The greater omentum (or epiplón mayor) is an Because of the discontinuous mesothelial lining anatomical structure resembling an apron, hanging on the milky spots, the glomerulus-like vascular in the peritoneal cavity, and usually extending over structures are exposed to the peritoneal cavity4. The a large area of the abdomen1 (Figure 1, 2). It arises normal venous drainage parallels the arteries and from the greater curvature of the stomach, it cross- empties into the portal system5. The gastroepiploic es the transverse colon and descends in front of ab- vein increases in diameter after receiving branches dominal viscera, covering the intestines. There are from stomach and omentum and empties into the two portions: the gastrocolic ligament, from the superior mesenteric vein (83%) or in the first part stomach to the transverse colon, and an area below of the splenic portal vein6. The terminal lymphat- the colon called apron (Figure 2). The omentum is ics form a web with irregular interconnections and composed of a frame of trabecular connective tis- with bulging saccular parts. This forms an unusual sue, intermingled with arteries, veins, lymphatics, pattern shaped like flattened tubes7. Some of the 1 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, eosinophil- ic granulocytes, mast cells). Fat cells are the most numerous cellular population, and their mass in- creases 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 meso- derm gives rise to multiple derivatives, including Figure 1. Scheme of the main constituents of the omentum (Reprinted from “The Greater Omentum”, 1983, Edited by the mesothelium - a layer of cells that remains as D. Liebermann-Meffert and H. White – with permission a lining of the abdominal cavity, pleura, medias- from Springer-Nature). tinum, and pericardium. The mesothelium lining 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. Lieb- ermann-Meffert and H. White – with permission from Springer-Nature). The greater omentum as a site for pancreatic islet transplantation 3 Figure 3. Vasculature of the Greater omentum in a human donor, imaged via angiography with barium gelatine. (Re- printed from “The Greater Omentum”, 1983, Edited by D. Liebermann-Meffert and H. White – with permission from Springer-Nature). 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). Figure 4. Adult human omentum from (a) a 36-year-old The portion of the dorsal mesentery that attaches donor with a lean omentum and (b) from a 69-year-old donor with heavy deposition of fat in the omentum. (Re- to the greater curvature of the stomach is known as printed from “The Greater Omentum”, 1983, Edited by D. the dorsal mesogastrium (Figure 5). This structure Liebermann-Meffert and H. White – with permission from subsequently expands, ‘balloons’ and then ‘deflates’, Springer-Nature). giving rise to an apron-like structure (a double layer of peritoneum) that is known as the greater unique structure of its microcirculatory system. omentum1. The rotation of the primitive stomach In pathological conditions, the omentum performs and the folding of the dorsal mesentery containing functions aimed at preserving body homeosta- the spleen and pancreas form a dependent large in- sis12,13. The omentum absorbs particles and has an ferior recess know as the lesser sac10. The greater important role in combating abdominal infections omentum is thus one of the omenta deriving from (Morison called it the “abdominal policeman”13). the folding of the peritoneum; it is located between During episodes of peritonitis, the omentum rapidly the greater sac (peritoneal cavity proper) and the clears bacteria and foreign material that have pen- lesser sac (omental bursa) of the abdominal cavity. etrated into the peritoneal cavity14. Effector mech- A fusion of the double layer of peritoneum most anisms are mediated by macrophages, neutrophils likely occurs, giving rise to the adult greater omen- and, probably, B-lymphocytes. Macrophages are tum11 (Figure 2). contained within the milky spots, and from there they can migrate into the peritoneal cavity via the PHYSIOLOGY, FUNCTION, AND PATHOPHYSIOLOGY openings in the mesothelial layer15. These macro- OF THE GREATER OMENTUM phages phagocyte particles and bacteria from the The physiological function of the omentum is still peritoneal cavity. Subsequently, neutrophils can be unclear but it is believed to be connected to the recruited from the circulation, extravasate in the 4 M. Pellicciaro, I. Vella, G. Lanzoni, G. Tisone, C. Ricordi Figure 5. Schematic of the human embryo showing the disposition of developing organs and the location of the dorsal mesogastrium, that will give rise to the greater omentum. milky spots and exudate in the peritoneal cavity studies show that the exchange flows are extreme- to perform anti-microbial functions16,17. The omen- ly efficient, if not the most efficient among those tal functions of adhesiveness and cohesiveness observed in the human body22. Under steady-state are fundamental during mechanical trauma, tissue conditions, most of the fluid passing the capillary ischemia, intra-abdominal infections or reduced barrier in the omentum seems to become lymph. peristalsis18. Injury to the serosal membranes caus- Hence, the liquid originating from the omental mi- es an immediate exudation of albumin, globulin, crocirculation does not return directly to the blood and fibrinogen that, once activated, become fibrin. but passes through the lymphatic system. 3 hours after the exudative phase, the adhesion phase starts. This