Biology Colloquium - Dr. Talitha van der Meulen

Biology Colloquium - Dr. Talitha van der Meulen

Postby cdouglas » Mon Mar 18, 2013 7:36 am

California State University, Fresno
Department of Biology Presents

“Urocortin 3 as a Marker for Mature Human Primary and Embryonic Stem Cell-Derived Pancreatic Alpha and Beta Cells ”

Dr. Talitha van der Meulen
Clayton Laboratories for Peptide Biology
The Salk Institute for Biological Studies

Friday, March 22, 2013
3:00-4:00 PM
Science 2, Room 109

Type 1 diabetes (T1D) continues to affect millions world-wide, with the incidence of the disease rising and the age of onset dropping. Despite considerable progress in the treatment and management of the disease, a cure for T1D has not been identified. Strategies to restore functional beta cell mass include pancreas transplants, requiring major surgery, or islet transplants in a relatively minor procedure. Nevertheless, the life-long requirement for immune suppression and the fact that graft function in many patients declines over time, coupled to the limited availibility of donor islets highlight the inherent limitations of the application of this approach to the T1D population at large. Embryonic stem (ES) cells overcome these limitations by potentially supplying unlimited numbers of cells for transplantation. The discovery that human ES cells can be differentiated into definitive endoderm and subsequently into hormone positive cells by recapitulating steps from embryonic development in vitro brings the prospect of generating stem cell-derived beta cells closer to reality.

Nevertheless, the generation of glucose-responsive beta cells from these definitive endoderm cells has proven difficult. Encouragingly, pancreatic endoderm precursor cells that were transplanted into immune compromised mice did differentiate into fully mature beta cells over time, suggesting that the pancreatic endoderm generated under current protocols can generate the precursor cells correctly. Ideally cells that are transplanted are fully differentiated to reduce the risk of teratoma formation, but until recently no marker was available to separate the glucose responsive beta cells from the non-glucose responsive insulin positive cells, hampering efforts to optimize protocols for the generation of these cells or to isolate them out of the total pool of cells. We recently discovered that the peptide hormone urocortin 3 marks mature glucose-responsive beta cells in mice and man as well as mature alpha cells in man. This identifies urocortin 3 as a suitable marker to instruct the identification of key steps towards generating mature, functional beta cells from pancreatic endoderm in a dish.

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