Mesothelial cell transplantation in models of acute inflammation and chronic peritoneal dialysis
Jazyk: | angličtina |
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Rok vydání: | 2003 |
Předmět: |
Inbred F344
Cell Transplantation/methods Epithelium/transplantation Animal Peritoneal Dialysis/adverse effects Inflammation/complications Dialysis Solutions/adverse effects Peritoneum/injuries Chronic/therapy Rats Kidney Failure Models Acute Disease Animals Female Genetic Therapy/methods Epithelial Cells/transplantation Peritonitis/chemically induced |
Zdroj: | Peritoneal dialysis international. 23(4):323-330 |
ISSN: | 0896-8608 |
Popis: | 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 beta-galactosidase (beta-Gal) was visualized by X-Gal staining of excised tissues. Quantification of the percent area of beta-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 differences 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. |
Databáze: | OpenAIRE |
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