Development and preclinical assessment of a bioartificial pancreas.

Details

Serval ID
serval:BIB_04BDC79A519E
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Development and preclinical assessment of a bioartificial pancreas.
Journal
Swiss medical weekly
Author(s)
Thorens B.
ISSN
1424-7860 (Print)
ISSN-L
0036-7672
Publication state
Published
Issued date
02/03/2007
Peer-reviewed
Oui
Volume
137
Number
Suppl 155
Pages
68S-71S
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Review
Publication Status: ppublish
Abstract
Transplantation of insulin secreting cells is regarded as a possible treatment for type 1 diabetes. One major difficulty in this approach is, however, that the transplanted cells are exposed to the patient's inflammatory and autoimmune environment, which originally destroyed their own beta-cells. Therefore, even if a good source of insulin-secreting cells can be identified for transplantation therapy, these cells need to be protected against these destructive influences. The aim of this project was to evaluate, using a clonal mouse beta-cell line, whether genetic engineering of protective genes could be a viable option to allow these cells to survive when transplanted into autoimmune diabetic mice. We demonstrated that transfer of the Bcl-2 anti-apoptotic gene and of several genes specifically interfering with cytokines intracellular signalling pathways, greatly improved resistance of the cells to inflammatory stresses in vitro. We further showed that these modifications did not interfere with the capacity of these cells to correct hyperglycaemia for several months in syngeneic or allogeneic streptozocin-diabetic mice. However, these cells were not protected against autoimmune destruction when transplanted into type 1 diabetic NOD mice. This suggests that in addition to inflammatory attacks by cytokines, autoimmunity very efficiently kills the transplanted cells, indicating that multiple protective mechanisms are required for efficient transplantation of insulin-secreting cells to treat type 1 diabetes.

Keywords
Animals, Bioartificial Organs, Clone Cells, Diabetes Mellitus, Type 1/therapy, Genes, bcl-2/physiology, Insulin-Secreting Cells/transplantation, Interferon-gamma/metabolism, Interleukin-1/metabolism, Mice, Mice, Inbred NOD, Pancreas, Artificial, Signal Transduction/physiology, Tissue Engineering
Pubmed
Create date
24/01/2008 13:41
Last modification date
20/08/2019 12:26
Usage data