Cell-Cell Interactions Promote Differentiation of Human Embryonic Stem Cells to Insulin-Secreting Cells

Funding Type: 
SEED Grant
Grant Number: 
RS1-00379
Investigator: 
ICOC Funds Committed: 
$0
oldStatus: 
Closed
Public Abstract: 
One million people in the United States have insulin dependent diabetes - a disease that elevates blood glucose and may result in kidney failure, blindness and amputation. Transplantation of insulin-producing beta cells can establish normal blood sugar levels without the need for insulin injections but multiple doses of cells are required and diabetes returns within 2-3 years in most islet transplant patients. This failure with time is thought to be primarily from “exhaustion” and other insults to an inadequate number of engrafted beta cells. If an abundant source of beta cells was available, long-term success would likely improve. Human embryonic stem cells are a promising source of beta cells for transplantation. A specific cell line of “pluripotential” stem cells differentiates into forerunners of beta cells. The forerunner cells do not make insulin but they can be identified and, when transplanted together with embryonic pancreas or blood vessel cells, will transform into insulin-producing cells. Prior studies have accomplished this transformation only after transplantation in rodents - in vivo - where the insulin-producing cells are not accessible for easy study or harvest for transplantation. We plan to isolate and grow human forerunner cells in the laboratory then mix them in a Petri dish with appropriate cells to coax them into becoming insulin-secreting cells. Once we have an ongoing colony of transformed insulin-producing cells, we will transplant them into diabetic mice (a strain that does not reject human tissue) to assess their ability to reverse insulin-dependent diabetes. These human embryonic stem cell investigations will deepen our understanding of stem cell biology and, potentially, lead to successful long-term treatment of insulin dependent diabetes.
Statement of Benefit to California: 
One million people in the United States have insulin dependent diabetes - a disease that elevates blood glucose and may result in kidney failure, blindness and amputation. Transplantation of insulin-producing beta cells can establish normal blood sugar levels without the need for insulin injections but multiple doses of cells are required and diabetes returns within 2-3 years in most islet transplant patients. This failure with time is thought to be primarily from “exhaustion” and other insults to an inadequate number of engrafted beta cells. If an abundant source of beta cells was available, long-term success would likely improve. Human embryonic stem cells are a promising source of beta cells for transplantation. A specific cell line of “pluripotential” stem cells differentiates into forerunners of beta cells. The forerunner cells do not make insulin but they can be identified and, when transplanted together with embryonic pancreas or blood vessel cells, will transform into insulin-producing cells. Prior studies have accomplished this transformation only after transplantation in rodents - in vivo - where the insulin-producing cells are not accessible for easy study or harvest for transplantation. We plan to isolate and grow human forerunner cells in the laboratory then mix them in a Petri dish with appropriate cells to coax them into becoming insulin-secreting cells. Once we have an ongoing colony of transformed insulin-producing cells, we will transplant them into diabetic mice (a strain that does not reject human tissue) to assess their ability to reverse insulin-dependent diabetes. These human embryonic stem cell investigations will deepen our understanding of stem cell biology and, potentially, lead to successful long-term treatment of insulin dependent diabetes. The proposed research will improve our understanding of stem biology; specifically, how stem cells become insulin-secreting cells. This work will enhance California's standing as a leader in cutting-edge stem cell research, a position that will translate into economic gains through the stimulation of biotechnology investment and scientific endeavor. For citizens of California with insulin dependent diabetes this work could ultimately led to an effective treatment through the transplantation of insulin-secreting cells or, perhaps, the regeneration of patients' own damaged beta cells.

© 2013 California Institute for Regenerative Medicine