Despite intense efforts over the past 30 years, human pancreatic beta cell lines have not been available. Here, the authors describe a robust technology for producing a functional human beta cell line using genetic modification of human fetal tissue. Genetically modified pancreatic buds were grafted into immunodeficient mice so that they could develop into mature pancreatic tissue. Upon differentiation, the newly formed beta cells proliferated. The resulting beta cells expanded in vitro to generate cell lines. One of these cell lines expressed many beta cell-specific markers without any substantial expression of markers of other pancreatic cell types. The cells secreted insulin when stimulated by glucose, and cell transplantation reversed chemically induced diabetes in mice. These cells represent a unique tool for large-scale drug discovery and provide a preclinical model for cell replacement therapy in diabetes. This technology could be generalized to generate other human cell lines when the cell type-specific promoter is available.
Ravassard, P., et al. (2011). A genetically engineered human pancreatic beta cell line exhibiting glucose-inducible insulin secretion. J Clin Invest. 121(9):3589-97.
Ramifications for Individuals with Type 1 Diabetes:
A human beta cell line is incredibly valuable for further understanding islet biology, beta cell health and survival, and diabetes drug discovery. The success shown in this report should lead to the creation of additional human beta cell lines that will be even closer in resemblance to true human beta cells. It may also lead to another alternative source of beta cells as a transplantable product in beta cell replacement therapy.
This work, led by Dr. Scharmann at INSERM, was not directly supported by a JDRF but the work involves the Beta Cell Biology Consortium, which is funded by the NIH with the Special Diabetes Programs Funding.