Prevention of Detrimental Effect of Cyclosporin A on Vascular Ingrowth of Transplanted Pancreatic Islets With Verapamil

Author:

Rooth Pål1,Dawidson Ingemar1,Lafferty Kevin1,Diller Ken1,Armstrong John1,Pratt Phil1,Simonsen Randall1,Täljedal Inge-Bert1

Affiliation:

1. Department of Surgery, University of Texas Southwestern Medical Center at Dallas, Dallas; the Department of Biomedical Engineering, University of Texas Austin, Texas; the Barbara Davis Center for Childhood Diabetes Denver, Colorado; the Department of Histology and Cell Biology, University of Umea Umea, Sweden

Abstract

The revascularization of pancreatic islet clusters transplanted beneath the renal capsule was studied in a syngeneic mouse model. The degree of vascular ingrowth was visualized by in vivo fluorescence microscopy (fluorescein isothiocyanate-dextran) and judged by a semiquantitative method from coded video recordings. The recipients of isografts were divided into four groups, depending on their daily immunosuppressive treatment: 1) none (controls), 2) 15 mg/kg cyclosporin A (CsA), 3) 0.4 mg/kg verapamil + 15 mg/kg CsA, and 4) 20–30 mg/kg methylprednisolone. In control animals, capillary ingrowth was first demonstrated on day 6, followed by progressive vascularization up to day 34. After 6 mo, the vascular architecture was similar to that seen in normal islets in situ. CsA alone significantly decreased vascular ingrowth on day 14 compared with controls (P < .02). Verapamil prevented the detrimental effect of CsA (P < .01), probably by improving renal subcapsular blood flow. Methylprednisolone did not affect revascularization compared with control animals at day 14. We conclude that CsA inhibits vascular ingrowth into transplanted pancreatic islets, which is likely to have clinical implications. The prevention of CsA vascular ingrowth inhibition by a calcium antagonist indicates a possible approach to the correction of this problem, particularly when the renal capsule is used as the recipient's transplant site.

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

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