Therapeutic Applications of Mesothelial Cell Sheets

Abstract

Mesothelial cells are an integral part of the peritoneum and play an important role in maintaining its structural and functional properties. In recent years a number of studies on mesothelial cells have been performed to evaluate the localization, secretional properties and the ability of regeneration and transdifferentiation of these cells. They are also involved in the repair of the peritoneum damage following surgery or peritonitis. Mesothelial cells produce several cytokines, growth factors and extracellular matrix components, possessing anti-inflammatory and immunomodulatory properties. Based on previous research, cell sheet engineering has made it possible to transplant cells that retain the cells' function, and stacking different cells in layers has also become possible. Arranging blood vessels between the cell layers is a problem when stacking cells in layers. Whether adequate blood flow can be obtained for the cell layers to survive long-term is the difference between success and failure. Mesothelial cell transplantation for peritoneal regeneration needs to be performed under conditions in which the surface area of the visceral peritoneum is large and the mesothelial cell damage area is small. In this article we explain cell sheet engineering as one of the technologies for transplanting cells with a variety of intercellular adhesion and cell membrane molecules maintained intact, and its application to peritoneal regeneration.

Mesothelial cells and peritoneal homeostasis

“…By means of fluorescently labeling transplanted mesothelial cells, they were traced in a rat model of thioglycolate-induced peritonitis (79) and found to resurface denuded peritoneum and to home to milky spots of omental tissue and lymphatic stomata of the diaphragm. However, implantation of these cells also increased the inflammatory response, suggesting that there are limitations with this approach that will need to be addressed (80).…”

Stimulation of Peritoneal Mesothelial Cells to Secrete Matrix Metalloproteinase-9 (MMP-9) by TNF-α: A Role in the Invasion of Gastric Carcinoma Cells

“…In addition to matrix-degrading enzymes secreted by the cancer cells themselves, MMP-9 derived from the host microenvironments, including peritoneal mesothelial cells, appeared to contribute to the cancer cell invasion into submesothelial matrices (Figure 6). Although mesothelial cells were thought to play a structural role in maintaining the smooth surface of the peritoneum and possess rather static properties, recent studies have shown that mesothelial cells produce various growth factors (e.g., vascular endothelial growth factor, basic fibroblast growth factor, epidermal growth factor, hepatocyte growth factor, and transforming growth factor-β) and ECM components (e.g., cytokeratin, vimentin and type I and III collagen) [21]. Therefore, peritoneal mesothelial cells are considered to be potentially active cells that dynamically respond to environmental changes.…”

Human Omental Mesothelial Cells Impart an Immunomodulatory Landscape Impeding B- and T-Cell Activation

“…Several studies have also demonstrated that autologous peritoneal grafts efficiently prevented post-operative peritoneal adhesions [ 14 , 20 , 21 ]. As such, current developments in mesothelial-cell-based therapies are principally focusing on tissue engineering of autologous mesothelial cell sheets for the regeneration of the damaged mesothelium [ 5 , 22 , 23 ]. Notwithstanding, as the mesothelium also share morpho-structural and biochemical similarities with other simple epitheliums, mesothelial cells have also been highlighted as useful surrogate cells to regenerate the corneal endothelium, vascular endothelium, or synovium [ 24 , 25 , 26 , 27 ].…”