Dialysis – Transplantation

Kidney International (2005) 68, 2362–2367; doi:10.1111/j.1523-1755.2005.00698.x

Apparent successful mesothelial cell transplantation hampered by peritoneal activation

LIESBETH H P HEKKING, MACHTELD M ZWEERS, EELCO D KEUNING, BAS A J DRIESPRONG, DIRKDE WAART, ROBERT H J BEELEN and JACOB VAN DEN BORN

Department of Molecular Cell Biology and Immunology, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands; Department of Nephrology, Academic Medical Center, Amsterdam, The Netherlands; and Department of Clinical Chemistry, Academic Medical Center, Amsterdam, The Netherlands

Correspondence: Jacob van den Born, Ph.D., VU University Medical Center, Department of Molecular Cell Biology & Immunology, PO Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail: j.vandenborn@vumc.nl

Received 7 October 2004; Revised 1 April 2005; Re-revised 2 June 2005; Accepted 20 June 2005.

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Abstract

Apparent successful mesothelial cell transplantation hampered by peritoneal activation.

Background

 

Mesothelial cell transplantation has been suggested to improve mesothelial repair after surgery, recurrent peritonitis and peritoneal dialysis.

Methods

 

In this study we evaluated mesothelial cell transplantation during the resolution phase of experimentally thioglycollate-induced peritonitis in rats. To this end 4 times 106 DiO-labeled autologous mesothelial cells were transplanted 1 week after peritonitis induction. Peritoneal inflammation and permeability characteristics were evaluated after another week.

Results

 

Mesothelial cell transplantation after peritonitis resulted in incorporation of these cells in the parietal mesothelial lining, leading to an acute transient submesothelial thickening which was not seen in transplanted animals without prior peritonitis induction. Long-term functioning of these repopulated mesothelial cells leaded to peritoneal activation as evidenced by a approxtwofold increase in peritoneal lymphocytes (P < 0.01) and omental mast cell counts (P < 0.05), accompanied by the induction of inflammation markers monocyte chemoattractant protein-1 (MCP-1) (P < 0.01) and hyaluronan (P < 0.01) in the transplanted peritonitis group, but not in rats with peritonitis without mesothelial cell transplantation or in control rats without mesothelial cell transplantation (all four parameters P < 0.01). In addition, trapping of transplanted mesothelial cells in the milky spots of omental tissue and lymphatic stomata of the diaphragm both in control and thioglycollate rats seems to increase microvascular permeability, reflected by apparent increased diffusion rates of small solutes and proteins.

Conclusion

 

Altogether, our data underscore the importance of controlling peritoneal (patho)physiology and function in mesothelial transplantation protocols.

Keywords:

mesothelial cells, transplantation, peritonitis

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