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Time Course and Quantification of Pancreatic Islet Revasculariztion Following Intraportal Transplantation

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Abstract:

A large proportion of islets are lost after transplantation partly due to a lack of functional vasculature. Islets revascularize from host tissue but the process takes up to 2 weeks and has been suggested to result in reduced vascular density in engrafted islets. We describe a method for observing and quantifying the revascularization of intraportally transplanted islets that includes number, density, and branching of islet capillaries. Syngeneic islets were transplanted selectively into the two right posterior lobes of the liver of adult Lewis rats. Sections of the livers were dual stained for insulin and Bandeiraea simplicifolia and analyzed for islet morphology, area, and vascular density from day 0 to day 14 posttransplant and compared to native islets. Vascular density was 1431 ± 75.7 vessels/mm2 in native islets and fell to 325.3 ± 30.8 vessels/mm2 (p < 0.001) by day 1 posttransplant and subsequently increased until day 14 when it was significantly higher than in native islets (2612.5 ± 107.8 vessels/mm2, p < 0.001). The percentage of islet area occupied by vascular space was 9.1 ± 0.9% in native islets. After falling to 2.3 ± 0.3% (p < 0.001) 1 day posttransplant this rose to supranormal levels (21.5 ± 0.8%, p < 0.001) by day 14. The index of capillary branching was 0.771 ± 0.017 in native islets and fell to 0.465 ± 0.02 (p = 0.001) by day 3 but returned to native values by day 7 posttransplantation (0.726 ± 0.03). This technique provides a robust method for tracking and quantifying the revascularization of intraportally transplanted islets, which should enable the comparison of different strategies aimed at accelerating islet revascularization.

Keywords: Endothelium; Islet transplantation; Quantification; Vascular density

Document Type: Research Article

DOI: https://doi.org/10.3727/000000007783464993

Affiliations: 1: Centre for Nephrology, Royal Free Campus, Royal Free and University College Medical School, London, NW3 2PF, UK 2: Department of Endocrinology, Royal Free Campus, Royal Free and University College Medical School, London, NW3 2PF, UK 3: Department of Hepatology, Royal Free Campus, Royal Free and University College Medical School, London, NW3 2PF, UK

Publication date: 2007-05-01

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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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