Xenotransplantation of encapsulated insulin-producing pig cells [ 2011 - 2011 ]

Research Grant

Researchers: Prof Bernard Tuch (Principal investigator)

Brief description The ideal treatment for insulin-dependent diabetes is the replacement of insulin-producing cells. Currently, this is carried out using a whole pancreas or experimentally with cells isolated from the pancreas of donor humans. Despite the success of these procedures, demand for human organs far exceeds supply, thus driving the search for suitable alternatives. Pigs are physiologically similar to humans, and insulin-producing cells can be easily isolated from the fetal pig pancreas as islet-like cell clusters; 8% of the cells in the cluster produce insulin and the remaining cells develop this capability after transplantation. Transplantation requires chronic immunosuppression with drugs which increase the risk of infection and cancer. To many people with diabetes, the side effects will be greater than the potential benefit. Placing cells inside microcapsules made of a biologically inert material may prevent graft rejection without chronic immunosuppression. The Investigators have demonstrated that encapsulated insulin-producing pig cells survive and function when transplanted into diabetic immunodeficient mice, but not when xenografted into immunocompetent mice. It is hypothesised that this is due to an immunological or inflammatory response by the host in response to the shedding of molecules by the encapsulated pig cells. A pre-clinical model to test the efficacy of encapsulated insulin-producing pig cells is the humanized mouse. It is hypothesized that transient administration of anti-rejection drugs will be needed to allow the survival of pig cells xenografted into these mice and normalization of BGL once diabetes has been induced. The aims of this study are: 1. To assess the nature of the host response when encapsulated insulin-producing fetal pig cells are transplanted into diabetic BALB-c mice. 2. To normalize blood glucose levels (BGL) in diabetic humanized mice transplanted with encapsulated insulin-producing fetal pig cells.

Funding Amount $AUD 763,316.76

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant