OP-142 Gene Expression Profile of Nonfunctional Human Pancreatic Islets: Predictors of Transplant Failure?

Islet culture has become a standard part of most successful protocols for clinical islet transplantation. To date, however, islets are transplanted based on crude measures of viability, purity and in vitro insulin production without adequate prior assessment of the potential for in vivo function. Th...

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Bibliographic Details
Published in:Transplantation proceedings 2005-10, Vol.37 (8), p.3441-3443
Main Authors: Sabek, O.M., Marshall, D.R., Minoru, O., Fraga, D.W., Gaber, A.O.
Format: Article
Language:English
Subjects:
Adult
Animals
Biological and medical sciences
C-Peptide - blood
Child, Preschool
Female
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Gene Expression Profiling
Humans
Insulin-Like Growth Factor Binding Protein 5 - genetics
Islets of Langerhans - cytology
Islets of Langerhans Transplantation - physiology
Male
Medical sciences
Mice
Mice, Inbred NOD
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Tissue, organ and graft immunology
Transplantation, Heterologous
Vascular Endothelial Growth Factor A - genetics
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Summary:Islet culture has become a standard part of most successful protocols for clinical islet transplantation. To date, however, islets are transplanted based on crude measures of viability, purity and in vitro insulin production without adequate prior assessment of the potential for in vivo function. The purpose of this study was to define the gene expression profiles of human islets associated with in vivo function using a nonimmune NOD-scid mouse model. Human islets from eight isolations were maintained in culture for 7 to 14 days in Memphis serum-free media until transplanted. The RNA was extracted from 10,000 IEQ using RNASTAT-60. The gene expression profiles were analyzed using high-density Affymetrix U133A GeneChips and Genespring software. An aliquot of 2000 IEQ from each islet preparation was also transplanted into NOD-scid animals (n = 5) for in vivo function assessments. Islet function was assessed by measurements of human C-peptide at days 7 and 14 posttransplant. Human C-peptide levels were determined by radioimmunoassay. Gene analysis of nonfunction islets (4 of 8 islet preparations) showed high relative levels of expression of proinflammatory genes and low relative levels of genes directed toward insulin processing and secretion as well as islet integrity. Overexpression of hypoxia and proinflammatory genes may result in reduced insulin secretion and lead to islet destruction posttransplantation. Identifying and validating those genes could allow the development of a potency assay for human transplantation that would be very useful for screening human islet preparations before clinical transplant.
ISSN:0041-1345
1873-2623
DOI:10.1016/j.transproceed.2005.09.054