Research Group

  • Dr Jon Odorico, Principal Investigator
  • Dr William Burlingham, Co-Investigator
  • Dr Luis Fernandez, Collaborator
  • Dr Victoria Browning, Research Assistant
  • Dr Brenda Kahan, Research Assistant
  • Dr Deepika Rajesh, Research Assistant


  • University of Wisconsin, Madison, USA


  • Immune Responses to Human Pancreatic Progenitor Cells

Human embryonic stem cells (hESC) may one day be used as a source of pancreatic progenitor cells and/or b cells for transplantation into patients with type I diabetes mellitus. Several significant scientific challenges still confront this potential therapy, including production of functional insulin-producing cells and understanding how the immune system would respond to hESC-derived therapeutic cell populations. Here, our objective is to study how the human adaptive immune system recognizes and responds in vivo to an enriched, non-tumorforming population of hESC-derived pancreatic precursor cells, which express the homeodomain protein PDX1.

We have recently developed a novel culture protocol based in part on known signaling events in pancreas specification to promote hESC to differentiate into endoderm and proliferative PDX1+ pancreatic epithelia. In this project, we will test the hypothesis that human PDX1+ pancreatic progenitor cells stimulate a less vigorous immune response than normal adult islets by studying the adaptive immune responses to such cells in humanized mice.

Specific aim 1 is to determine the expression of HLA antigens and co-stimulatory molecules on PDX1+ pancreatic progenitor cells. In aim 2, human PDX1+ progenitors will be transplanted into mice previously conditioned to harbor a human immune system. Immune responses in recipients will be correlated with graft outcomes. Transplants of undifferentiated hESC and adult human islets will be studied in parallel. Restoration of b cell function by hESC-derived PDX1+ cells will also be examined after transplantation of graded doses under the kidney capsule in diabetic mice. In aim 3, we will examine whether progenitor cells can support the survival and function of a subtherapeutic mass of transplanted adult islets. Overall, these studies will test whether human PDX1+ cells stimulate an allogeneic adaptive immune response in vivo and provide a platform for restoration of lost b cell function.

Progress Report

Final Report