State of the Art on Autologous Mesothelial Transplant in Animals and Humans

2007 ◽  
Vol 30 (6) ◽  
pp. 456-476 ◽  
Author(s):  
N. Di Paolo ◽  
G. Sacchi ◽  
M.T. Del Vecchio ◽  
G. Nicolai ◽  
S. Brardi ◽  
...  
Keyword(s):  
Heart Disease ◽  
Peritoneal Dialysis ◽  
Progenitor Cells ◽  
State Of The Art ◽  
Mesothelial Cell ◽  
Mesothelial Cells ◽  
The Body ◽  
Review Of The Literature ◽  
Peritoneal Adhesions ◽  
Prevention And Treatment

Sixteen years ago rabbit and human mesothelial cells were successsfully cultured and autoimplanted. The aim of the study was merely to demostrate that mesothelial implant was possible and interesting not only in peritoneal dialysis, but also in the vaster field of medicine and surgery concerning all the mesothelial districts of the body. The aim of this paper is to recollect the steps which have led to autolougous mesothelial transplantation and verify if the tecnique has been validated and adopted by others. Review of the literature published in the last 15 years shows that intraperitoneal transplantation of mesothelial cells has been effective in reducing the formation of peritoneal adhesions, and in remodeling the area of mesothelial denudation. New studies on the mesothelial cell opened the way to costruction of transplantable tissue-engineered artificial peritoneum, to the utilization of mesothelial progenitor cells and to find simple metods to collect autologous mesothelial cells. Finally mesothelial trasnsplantation may represent a new neovascular therapy in the prevention and treatment of ischemic coronaric heart disease.

Continuous Mesothelial Injury and Regeneration during long Term Peritoneal Dialysis

1987 ◽  
Vol 7 (3) ◽  
pp. 148-156 ◽  
Author(s):  
Lazaro Gotloib ◽  
Abshalom Shostack ◽  
Phina Bar-Sella ◽  
Ricardo Cohen
Keyword(s):  
Peritoneal Dialysis ◽  
Connective Tissue ◽  
Peritoneal Fluid ◽  
Mesothelial Cell ◽  
Mesothelial Cells

This study reconstructs the whole sequence of mesothelial injury and regeneration in patients on longterm peritoneal dialysis. Our observations indicate that peritoneal dialysis induces a process of continuous mesothelial injury and regeneration. New mesothelial cells seem to originate from wandering mesothelial cells of the peritoneal fluid, as well as from mesothelial cell precursors localized in the sub-mesothelial connective tissue.

Cancer Antigen 1251S Locally Produced in the Peritoneal Cavity during Continuous Ambulatory Peritoneal Dialysis

1994 ◽  
Vol 14 (2) ◽  
pp. 132-136 ◽  
Author(s):  
Ger C.M. Koomen ◽  
Michiel G.H. Betjes ◽  
Oésirée Zemel ◽  
Raymond T. Krediet ◽  
Frans J. Hoek
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Peritoneal Cavity ◽  
Mesothelial Cell ◽  
Linear Increase ◽  
Mesothelial Cells ◽  
Ca 125 ◽  
Cancer Antigen ◽  
The Relationship

The local production of cancer antigen (CA) 125 in the peritoneal cavity of 14 continuous ambulatory peritoneal dialysis patients was studied. In addition, the relationship between the concentration of mesothelial cells and CA 125 in the peritoneal dialysate effluent was examined. The median results and ranges were as follows: plasma CA 125 14 U/mL (range 10 23), dialysate CA 125 18 U/mL (range 5.2 76), dialysate/plasma ratio 1. 9 (range 0.61 -5.4), and number of mesothelial cells 400/mL (range 10 5000). Peritoneal concentrations of mesothelial cellsand CA 125 were positively correlated (r = 0.50, p < 0.01). Using a monoclonal antibody, CA 125-positive cells were found in the cytospin preparations of the cells of dialysis effluents. All these CA 125 positive cells were also positive for cytokeratin used as a mesothelial cell marker. In vitro experiments using mesothelial cells in monolayers showed a linear increase in CA 125 concentration both in time and in relation to the number of mesothelial cells. From these experiments a production rate of 24 U/hour/1 06 cells could be calculated. It is therefore concluded that CA 125 is locally produced in the peritoneal cavity during CAPD and that the mesothelial cells are the major source of this CA 125.

Overnight Mesothelial Cell Exfoliation: A Magic Tool for Predicting Future Ultrafiltration Failure in Patients on Continuous Ambulatory Peritoneal Dialysis

2008 ◽  
Vol 28 (3_suppl) ◽  
pp. 107-113
Author(s):  
Talerngsak Kanjanabuch ◽  
Monchai Siribamrungwong ◽  
Rungrote Khunprakant ◽  
Sirigul Kanjanabuch ◽  
Piyathida Jeungsmarn ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Mesothelial Cell ◽  
Mesothelial Cells ◽  
Nutrition Status ◽  
Continuous Exposure ◽  
Peritoneal Membrane ◽  
Dialysis Solution ◽  
Ultrafiltration Failure

⋄ Background Continuous exposure of the peritoneal membrane to dialysis solutions during long-term dialysis results in mesothelial cell loss, peritoneal membrane damage, and thereby, ultrafiltration (UF) failure, a major determinant of mortality in patients on continuous ambulatory peritoneal dialysis (CAPD). Unfortunately, none of tests available today can predict long-term UF decline. Here, we propose a new tool to predict such a change. ⋄ Mesothelial cells from 8-hour overnight effluents (1.36% glucose dialysis solution) were harvested, co-stained with cytokeratin (a mesothelial marker) and TUNEL (an apoptotic marker), and were counted using flow cytometry in 48 patients recently started on CAPD. Adequacy of dialysis, UF, nutrition status, dialysate cancer antigen 125 (CA125), and a peritoneal equilibration test (3.86% glucose peritoneal dialysis solution) were simultaneously assessed and were reevaluated 1 year later. ⋄ Results The numbers of total and apoptotic mesothelial cells were 0.19 ± 0.19 million and 0.08 ± 0.12 million cells per bag, respectively. Both numbers correlated well with the levels of end dialysate–to–initial dialysate (D/D0) glucose, dialysate-to-plasma (D/P) creatinine, and sodium dipping. Notably, the counts of cells of both types in patients with diabetes or with high or high-average transport were significantly greater than the equivalent counts in nondiabetic patients or those with low or low-average transport. A cutoff of 0.06 million total mesothelial cells per bag had sensitivity of 1 and a specificity of 0.75 in predicting a further decline in D/D0 glucose and a sensitivity of 0.86 and a specificity of 0.63 to predict a further decline in UF over a 1-year period. In contrast, dialysate CA125 and other measured parameters had low predictive values. ⋄ Conclusions The greater the loss of exfoliated cells, the worse the expected decline in UF. The ability of a count of mesothelial cells to predict a future decline in UF warrants further investigation in clinical practice.

Biocompatibility of Peritoneal Dialysis Fluids: Long-term Exposure of Nonuremic Rats

2004 ◽  
Vol 24 (1) ◽  
pp. 37-47 ◽  
Author(s):  
Barbara Musi ◽  
Magnus Braide ◽  
Ola Carlsson ◽  
Anders Wieslander ◽  
Ann Albrektsson ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Growth Factor ◽  
Solute Transport ◽  
Transforming Growth Factor ◽  
Cell Damage ◽  
Mesothelial Cell ◽  
Mesothelial Cells ◽  
Vascular Density ◽  
Tissue Thickness

Objectives Long-term peritoneal dialysis (PD) leads to structural and functional changes in the peritoneum. The aim of the present study was to investigate the long-term effects of PD fluid components, glucose and glucose degradation products (GDP), and lactate-buffered solution on morphology and transport characteristics in a nonuremic rat model. Methods Rats were subjected to two daily intraperitoneal injections (20 mL/day) during 12 weeks of one of the following: commercial PD fluid (Gambrosol, 4%; Gambro AB, Lund, Sweden), commercial PD fluid with low GDP levels (Gambrosol trio, 4%; Gambro AB), sterile-filtered PD fluid (4%) without GDP, or a glucose-free lactate-buffered PD fluid. Punctured and untreated controls were used. Following exposure, the rats underwent a single 4-hour PD dwell (30 mL, 4% glucose) to determine peritoneal function. Additionally, submesothelial tissue thickness, percentage of high mesothelial cells (perpendicular diameter > 2 μm), vascular density, vascular endothelial growth factor (VEGF), and transforming growth factor (TGF) β1 mRNA expression were determined. Submesothelial collagen concentration was estimated by van Gieson staining. Results Submesothelial tissue thickness and vascular density, mediated by VEGF and TGFβ production, in the diaphragmatic peritoneum increased significantly in rats exposed to any PD fluid. Gambrosol induced a marked increased fibrosis of the hepatic peritoneum. A significant increase in high mesothelial cells was observed in the Gambrosol group only. Net ultrafiltration was reduced in the Gambrosol and in the glucose-free groups compared to untreated controls. Small solute transport was unchanged, but all groups exposed to fluids showed significantly increased lymph flow. Conclusions Our results show that long-term exposure to different components of PD fluids leads to mesothelial cell damage, submesothelial fibrosis, and neoangiogenesis. Mesothelial cell damage could be connected to the presence of GDP; the other changes were similar for all fluids. Peritoneal transport characteristics did not change in any consistent way and the neoangiogenesis observed was not paralleled by increased solute transport.

Mesothelial Cell Transplantation in Models of Acute Inflammation and Chronic Peritoneal Dialysis

2003 ◽  
Vol 23 (4) ◽  
pp. 323-330
Author(s):  
Liesbeth H.P. Hekking ◽  
V. Susan Harvey ◽  
Carin E.G. Havenith ◽  
Jacob van den Born ◽  
Robert H.J. Beelen ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Genetically Modified ◽  
Mesothelial Cell ◽  
Continuous Exposure ◽  
Peritoneal Fibrosis ◽  
Peritoneal Adhesions ◽  
Peritoneal Surface ◽  
Baxter Healthcare ◽  
Excised Tissues ◽  
Percent Area

♦ Objectives Mesothelial cell (MC) injury caused by continuous exposure to unphysiological peritoneal dialysis (PD) fluid and by episodes of peritonitis can eventually lead to peritoneal adhesions and peritoneal fibrosis. In the present study, we evaluated the possibility of using autologous genetically modified MCs for transplantation after the induction of peritoneal injury by acute inflammatory mediators or chronic instillation of PD fluid. ♦ Methods Rats were injected intraperitoneally either once with N-formyl-methionyl-leucyl-phenylalanine (fMLP), or thioglycollate, or PD fluid [ i.e., Dianeal (Baxter Healthcare, Deerfield, Illinois, USA) or Physioneal (Baxter, Nivelles, Belgium)], or chronically (up to 8 weeks) with Dianeal. From 2 to 48 hours later, animals were injected with syngeneic MCs genetically modified to express the LacZ reporter gene. Rats were sacrificed 2 days later and expression of β-galactosidase (β-Gal) was visualized by X-Gal staining of excised tissues. Quantification of the percent area of β-Gal–positive MCs on part of the parietal peritoneum was performed using computerized image analysis. ♦ Results The highest numbers of repopulated genetically modified MCs were observed 8 hours after a single thioglycollate injection, approximately 0.66% of a representative 2-cm2 area selected for study (corresponding to approximately 10% of the peritoneal surface). The number of genetically modified MCs found to repopulate the peritoneal surface following short-term injury varied with inflammatory mediator (thioglycollate > PD fluid > fMLP) and duration of exposure. No obvious difference's were observed between the two PD fluids tested. Reimplantation of syngeneic genetically modified MCs was also observed after chronic instillation of PD fluid. ♦ Conclusions These data demonstrate that transplanted genetically modified MCs repopulate the denuded areas on the peritoneal surface that were caused by acute or chronic inflammation. This technique opens possibilities of MC transplantation and gene therapy in order to prevent complications relevant to the continuous ambulatory PD setting.

scholarly journals Hyperbranched Polyglycerol is an Efficacious and Biocompatible Novel Osmotic Agent in a Rodent Model of Peritoneal Dialysis

2013 ◽  
Vol 33 (1) ◽  
pp. 15-27 ◽  
Author(s):  
Asher A. Mendelson ◽  
Qiunong Guan ◽  
Irina Chafeeva ◽  
Gerald A. da Roza ◽  
Jayachandran N. Kizhakkedathu ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Flow Cytometric Analysis ◽  
Mesothelial Cell ◽  
Mesothelial Cells ◽  
Rodent Model ◽  
Water Soluble ◽  
Control Group ◽  
Sprague Dawley ◽  
Hyperbranched Polyglycerol

♦ObjectivesTo enhance the effectiveness of peritoneal dialysis (PD), new biocompatible PD solutions may be needed. The present study was designed to test the efficacy and biocompatibility of hyperbranched polyglycerol (HPG)—a nontoxic, nonimmunogenic water-soluble polyether polymer—in PD.♦MethodsAdult Sprague–Dawley rats were instilled with 30 mL HPG solution (molecular weight 3 kDa; 2.5% – 15%) or control glucose PD solution (2.5% Dianeal: Baxter Healthcare Corporation, Deerfield, IL, USA), and intraperitoneal fluid was recovered after 4 hours. Peritoneal injury and cellular infiltration were determined by histologic and flow cytometric analysis. Human peritoneal mesothelial cells were assessed for viability in vitro after 3 hours of PD fluid exposure.♦ResultsThe 15% HPG solution achieved a 4-hour dose-related ultrafiltration up to 43.33 ± 5.24 mL and a dose-related urea clearance up to 39.17 ± 5.21 mL, results that were superior to those with control PD solution ( p < 0.05). The dialysate-to-plasma (D/P) ratios of urea with 7.5% and 15% HPG solution were not statistically different from those with control PD solution. Compared with fluid recovered from the control group, fluid recovered from the HPG group contained proportionally fewer neutrophils (3.63% ± 0.87% vs 9.31% ± 2.89%, p < 0.0001). Detachment of mesothelial cells positive for human bone marrow endothelial protein 1 did not increase in the HPG group compared with the stain control ( p = 0.1832), but it was elevated in the control PD solution group (1.62% ± 0.68% vs 0.41% ± 0.31%, p = 0.0031). Peritoneal biopsies from animals in the HPG PD group, compared with those from control PD animals, demonstrated less neutrophilic infiltration and reduced thickness. Human peritoneal mesothelial cell survival after HPG exposure was superior in vitro ( p < 0.0001, 7.5% HPG vs control; p < 0.01, 15% HPG vs control). Exposure to glucose PD solution induced cytoplasmic vacuolation and caspase 3–independent necrotic cell death that was not seen with HPG solution.♦ConclusionsOur novel HPG PD solution demonstrated effective ultrafiltration and waste removal with reduced peritoneal injury in a rodent model of PD.

HSP-Mediated Cytoprotection of Mesothelial Cells in Experimental Acute Peritoneal Dialysis

2010 ◽  
Vol 30 (3) ◽  
pp. 294-299 ◽  
Author(s):  
Thorsten O. Bender ◽  
Michael Böhm ◽  
Klaus Kratochwill ◽  
Hans Lederhuber ◽  
Michaela Endemann ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Stress Response ◽  
Mesothelial Cell ◽  
Lactic Dehydrogenase ◽  
Mesothelial Cells ◽  
Cellular Stress Response ◽  
Protein Loss ◽  
Promising Therapeutic Approach

♦ BackgroundLow biocompatibility of peritoneal dialysis solution (PDS) injures mesothelial cells but also induces heat shock proteins (HSP), the main effectors of the cellular stress response. This study investigated whether overexpression of HSP upon pharmacologic induction results in cytoprotection of mesothelial cells in experimental PD.♦ MethodsStress response of mesothelial cells upon exposure to PDS was pharmacologically manipulated using glutamine as a co-inducer. In vitro, HSP-mediated cytoprotection was assessed by simultaneous measurements of HSP expression using Western blot analysis and viability testing using release of lactic dehydrogenase in cultured human mesothelial cells. In vivo, detachment of mesothelial cells from their peritoneal monolayer was assessed following exposure to PDS with and without the addition of glutamine in the acute rat model of PD.♦ ResultsIn vitro, mesothelial cell viability following exposure to PDS was significantly improved upon pharmacologic co-induction of HSP expression by glutamine (226% ± 29% vs 190% ± 19%, p = 0.001). In vivo, mesothelial cell detachment during exposure to PDS was reduced upon pharmacologic induction of HSP expression by glutamine (93 ± 39 vs 38 ± 38 cells, p = 0.044), resulting in reduced peritoneal protein loss (75 ± 7 vs 65 ± 4 mg, p = 0.045).♦ ConclusionOur results represent the first study of pharmacologic manipulation of HSP expression for cytoprotection of mesothelial cells following acute in vitro and in vivo exposure to PDS. PDS with added glutamine might represent a promising therapeutic approach against low biocompatibility of PDS but needs validation in a chronic PD model.

Isolation and Propagation in Vitro of Peritoneal Mesothelial Cells

1989 ◽  
Vol 9 (4) ◽  
pp. 341-347 ◽  
Author(s):  
J. Thomas Hjelle ◽  
Barbara T. Golinska ◽  
Diane C. Waters ◽  
Kevin R. Steidley ◽  
David R. McCarroll ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Cell Biology ◽  
Life Support ◽  
Cultured Cells ◽  
Mesothelial Cell ◽  
Experimental System ◽  
Mesothelial Cells ◽  
Growth Media ◽  
Peritoneal Mesothelial Cells

Mesothelial cells lining the peritoneal cavity are the primary site of molecular exchange during peritoneal dialysis, a life support system for over 50 000 patients worldwide. In this study, techniques are described for the isolation and propagation in culture of peritoneal mesothelial cells from rats and rabbits. For comparison, mesothelial cells were also obtained from the serosal surface of human colonic tissue. By electron microscopy the cultured cells were found to exhibit microvilli, a well developed endoplasmic reticulum and golgi apparatus, micropinocytotic vesicles, and lipid-filled intracellular vesicles. Immunochemical probes revealed the expression by these cells in vitro of cytokeratin, fibronectin, vimentin, and keratin, but not von Willebrand factor. Mesothelial cells from rat, rabbit, and human exhibited contact inhibition, but differences in growth rates and dependence on supplements to the growth media. This work provides a multispecies comparison of the behavior of mesothelial cells in vitro for the purpose of developing an experimental system for the study of mesothelial cell biology and the role of these cells in peritoneal dialysis.

Biocompatibility Reduces Inflammation-Induced Apoptosis in Mesothelial Cells Exposed to Peritoneal Dialysis Fluid

2015 ◽  
Vol 39 (1-3) ◽  
pp. 200-209 ◽  
Author(s):  
Beatriz Santamaría ◽  
Alvaro Conrado Ucero ◽  
Alberto Benito-Martin ◽  
Maria Jesús Vicent ◽  
Mar Orzáez ◽  
...  
Keyword(s):  
Cell Death ◽  
Peritoneal Dialysis ◽  
Inflammatory Cytokines ◽  
Mesothelial Cell ◽  
Major Complication ◽  
Interferon Γ ◽  
Mesothelial Cells ◽  
Tnf Α ◽  
Peritoneal Dialysis Fluid ◽  
Induced Apoptosis

Background/Aims: Peritonitis is a major complication that arises out of peritoneal dialysis (PD), leading to death and loss of mesothelium and peritoneal injury, which may impede PD. We studied the combined impact of inflammatory mediators and PD fluids on mesothelial cell death. Methods: Cultured human mesothelial cells. Results: Inflammatory cytokines (TNF-α and interferon-γ) cooperate with bioincompatible PD fluids containing high glucose degradation product (GDP) concentrations to promote mesothelial cell death. Thus, the inflammatory cytokine cocktail induced a higher rate of death in cells cultured in high GDP PD fluid than in low GDP PD fluid or cell culture medium (cell death expressed as % hypodiploid cells: TNF-α and interferon-γ in RPMI: 14.15 ± 1.68, TNF-α and interferon-γ in 4.25% low GDP PD fluid 13.16 ± 3.29, TNF-α and interferon-γ in 4.25% high GDP PD fluid 25.88 ± 2.18%, p < 0.05 vs. the other two groups). BclxL BH4 peptides, Apaf-1 inhibition or caspase inhibition failed to protect from apoptosis induced by the combination of inflammatory cytokines and bioincompatible PD fluids, although they protected from other forms of mesothelial cell apoptosis. Conclusion: Inflammation cooperates with high GDP PD fluids to promote mesothelial cell death, which is resistant to several therapeutic approaches. This information provides a framework for selection of PD fluid during peritonitis.

scholarly journals Pathophysiology of the Peritoneal Membrane during Peritoneal Dialysis: The Role of Hyaluronan

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Susan Yung ◽  
Tak Mao Chan
Keyword(s):  
Peritoneal Dialysis ◽  
Cell Function ◽  
Mesothelial Cell ◽  
Protective Role ◽  
Mesothelial Cells ◽  
Cell Phenotype ◽  
Peritoneal Membrane ◽  
Structural Support

During peritoneal dialysis (PD), constant exposure of mesothelial cells to bioincompatible PD solutions results in the denudation of the mesothelial monolayer and impairment of mesothelial cell function. Hyaluronan, a major component of extracellular matrices, is synthesized by mesothelial cells and contributes to remesothelialization, maintenance of cell phenotype, and tissue remodeling and provides structural support to the peritoneal membrane. Chronic peritoneal inflammation is observed in long-term PD patients and is associated with increased hyaluronan synthesis. During inflammation, depolymerization of hyaluronan may occur with the generation of hyaluronan fragments. In contrast to native hyaluronan which offers a protective role to the peritoneum, hyaluronan fragments exacerbate inflammatory and fibrotic processes and therefore assist in the destruction of the tissue. This paper will discuss the contribution of mesothelial cells to peritoneal membrane alterations that are induced by PD and the putative role of hyaluronan in these processes.

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