BCBC Consortium aims to develop cell-based therapy for insulin delivery

NIH-funded Beta Cell Biology Consortium aims to eliminate daily insulin injections, finger pricks

Oregon Health & Science University's Markus Grompe, M.D., will lead a multi-center team of scientists selected to participate in the prestigious Beta Cell Biology Consortium (BCBC). Funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the consortium's long-term goal is to develop a cell-based therapy for insulin delivery in type 1 diabetes patients.

"The goal of our work is to produce abundant quantities of functional human insulin-producing beta cells that can be used for transplantation to cure patients with type 1 diabetes. Our group in particular is focused on novel sources for transplantable beta cell replacements," said Grompe, principal investigator and director of the Pap- Family Pediatric Research Institute, OHSU Doernbecher Children's Hospital; and director of the Oregon Stem Cell Center at OHSU.

Type 1 diabetes, formerly called juvenile diabetes, is characterized by a lack of insulin that results from the destruction of the insulin-producing beta cells of the pancreas. Without insulin, the body cannot process the glucose it receives from food and requires for energy. People with type 1 diabetes must take insulin every day, either by injection or continuously through a pump. To ensure they are receiving the proper amount, they frequently test their blood-glucose levels, which requires multiple finger pricks throughout the day.

"It is our hope that through the work of this interactive consortium, we can eliminate the need for this painful, lifelong ritual," said Grompe.

Grompe is a nationally accomplished stem cell and gene therapy expert. His pioneering work on liver stem cells and liver regeneration medicine provided a natural segue to this line of research. Recent studies by Grompe, BCBC project co-investigator Philip Streeter, Ph.D., and others indicate adult liver cells can successfully be converted into insulin-producing beta cells through genetic reprogramming in a mouse model. However, it is not yet know which liver cells can best be transformed into beta cells, and existing methods for growing liver cells in tissue culture are not well developed, according to Grompe.

With the support of this and similar grants, Grompe and colleagues are working to determine which type of liver cell is most easily converted and perfecting their methods of growing them in tissue culture. In addition, they are exploring the potential for harvesting and manipulating cells from novel sources, including the gall bladder.

"We have found that human gall bladder cells, which are very similar to the cells within the liver, can be grown and expanded in tissue culture very easily. It is a very promising source of reprogrammable beta cells," explained Grompe, who also is a professor of pediatrics and molecular and medical genetics in the OHSU School of Medicine, OHSU Doernbecher Children's Hospital.

Investigators working on the "Novel Sources of Transplantable Beta-Cell Replacements" project include: Grompe; Streeter, an associate professor of pediatrics, Pap- Family Pediatric Research Institute, OHSU Doernbecher Children's Hospital, and member of the Oregon Stem Cell Center at OHSU; Klaus Kaestner, Ph.D., University of Pennsylvania, Philadelphia, Pa.; Mark Kay, M.D., Ph.D., Stanford University, Palo Alto, Calif.

OHSU has licensed technology to Novus and Stemgent, of which Drs. Grompe and Streeter are inventors. The technology will be used in this research. This potential individual and institutional conflict of interest has been reviewed and managed by OHSU.