Project

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Development and preclinical assessment of a bioartificial pancreas

Applicant Thorens Bernard
Number 58682
Funding scheme NRP 46 Implants and Transplants
Research institution Département de Pharmacologie & Toxicologie Faculté de Biologie et de Médecine Université de Lausanne
Institution of higher education University of Lausanne - LA
Main discipline Molecular Biology
Start/End 01.01.2001 - 31.12.2003
Approved amount 415'972.00
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All Disciplines (2)

Discipline
Molecular Biology
Endocrinology

Lay Summary (English)

Lead
Lay summary
Development and Preclinical Assessment of a Bioartificial Pancreas

Background
A bioartificial pancreas consists of properly functioning glucose-regulated insulin secreting cells placed in an encapsulation device. The possibility to transplant such an bioartificial organ in type I diabetic patients is widely thought to be the solution for the treatment of this disease, to avoid in particular the development of long-term micro- and macrovascular complications.

Problem
The development of a bioartificial pancreas, however, is progressing slowly.
because of the use of pancreatic islets of human or pig origin. The complexity of these cellular preparations and the variability of their purity and functional state make it very difficult to interpret results of any transplantation experiment. In fact, failure of graft acceptance may be influenced by each of the cellular parameters, in addition to those associated with the host response.

Objective
The project proposes to rigorously evaluate the parameters that may allow the successful development and use of a bioartificial pancreas.

Approach
In thew first place, a well defined insulin secreting cell line, the ßTC-Tet cells, will be used. These insulin secreting cells are perfectly glucose regulated and their proliferation can be controlled by an easily controllable genetic switch. These cells can correct diabetic hyperglycemia, when transplanted under the kidney capsule of syngeneic or allogeneic mice. Furthermore, they can be genetically modified without losing their unique functional properties and will thus be used to evaluate the effects of genetic modifications to enable them to survive in an autoimmune (NOD mice) or xenogeneic (rat) environment. The requirement for additional protection, in particular against direct cellular contact with inflammatory or immune cells, will be tested by means of cellular encapsulation. The encapsulation techniques to be used for these studies will include alginate-poly-L-lysine microbeads, thermoplastic-based flat sheet and vascular devices.

As the ultimate insulin secreting cell lines to be used in a bioartificial pancreas should be of human origin, the project will, in parallel, attempt the conditional immortalization of human ßcells.
Direct link to Lay Summary Last update: 21.02.2013

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