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Open Access Endothelial Colony-Forming Cell Coating of Pig Islets Prevents Xenogeneic Instant Blood-Mediated Inflammatory Reaction

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Abstract:

Instant blood-mediated inflammatory reaction (IBMIR) causes rapid islet loss in islet transplantation. Endothelial colony-forming cells (ECFCs) display unique abilities to promote angiogenesis and repair vascular injury compared to those of endothelial cells (ECs), which inhibits the allogeneic and xenogeneic IBMIR. We investigated the coating of pig islets with ex vivo-expanded ECFCs as a strategy to overcome xenogeneic IBMIR. Porcine islets were cocultured with human ECFCs in a specially modified culture medium for 2 days to obtain 70‐90% coverage. The coating of pig islets with human ECFCs did not affect the glucose-stimulated insulin secretion capacity or diabetes reversal rate after the transplantation of a marginal islet mass under the kidney capsules of diabetic nude mice compared to that of untreated islets. Uncoated islets, PBS control without islets, and the ECFC-coated islets were examined with an in vitro tubing loop assay using human blood. After 60 min of incubation in human blood, the ECFC-coated islets showed platelet consumption inhibition and low C3a and TAT assay results compared to those of the uncoated islets. Furthermore, there was very little macroscopic or microscopic clotting in the human ECFC-coated pig islets. The protective effect was more prominent compared to that of human EC coating of pig islets in our previous study. We investigated the changes in human-specific MCP-1, IL-8, and tissue factor (TF) levels after the coating of pig islets with human ECFCs or human ECs. The IL-8 levels after coating pig islets with ECFCs were significantly lower than those after coating pig islets with ECs, but there were no significant differences in the MCP-1 or TF levels between the ECFCs and ECs. In conclusion, the coating of pig islets with ECFCs completely prevented all components of xenogeneic IBMIR. ECFCs may be a better source of protection against xenogeneic IBMIR than are mature ECs.

Keywords: Endothelial cells (ECs); Endothelial colony-forming cells (ECFCs); Islet; Pig

Document Type: Research Article

DOI: https://doi.org/10.3727/096368911X566154

Affiliations: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

Publication date: 2011-11-01

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  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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