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Expression of Transforming Growth Factor- by Human Islets: Impact on Islet Viability and Function

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Abstract:

Transforming growth factor-1 (TGF-1) is a pleotropic cytokine that promotes angiogenesis and extracellular matrix protein synthesis in addition to its immunosuppressive effects. The purpose of this study is to identify optimal conditions for in vivo expression of TGF-1 by human islets to exploit the possible beneficial effects and minimize undesirable side effects. We transduced human islets with adenoviral vectors encoding the active form of Ad-TGF-1 or Ad-LacZ to test the effects of TGF-1 gene expression on islet in vivo function following their transplantation into a NOD-SCID mouse model. Islets were transduced with multiplicity of infection (MOI) of 20, 10, 5, and 2.5 per islet cell. At a MOI ranging from 2.5 to 20, expression of TGF-1 in islet supernatant persisted for 1–2 months and ranged from 153 ± 5 to 2574 ± 1299 pg/ml, respectively. Transduction with the lowest MOI (2.5) did not compromise the in vivo production of human C-peptide. We conclude that TGF-1 expression in transplanted islets does not compromise viability and that adenoviral transduction with the TGF-1 gene has a dose-dependent effect, with larger MOIs being deleterious. The data also indicate that in vitro culture system and the in vivo NOD-SCID model could be used successfully to evaluate the nonimmune effects of gene transduction.

Keywords: Ad-TGF-1; Human islets; NOD-SCID; Viability

Document Type: Research Article

DOI: https://doi.org/10.3727/000000007783465217

Affiliations: 1: Department of Surgery, Methodist Hospital/Cornell University, Physicians Organization, Houston, TX, USA 2: Environmental Health and Safety, St. Jude Children's Research Hospital, Memphis, TN, USA 3: Department of Surgery, Division of Transplantation, University of Tennessee, Memphis, TN, USA

Publication date: 2007-08-01

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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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