Every path in the search to find a cure for type 1 diabetes leads to beta cells. Type 1 occurs because an autoimmune attack has destroyed the insulin-producing beta cells in the pancreas — a cure cannot happen until we find a way to replace or replenish the body’s own insulin-producing capability.
Susan Bonner-Weir, PhD, Senior Investigator in Islet Cell and Regenerative Biology at Joslin and Professor of Medicine at Harvard Medical School has spent her career figuring out how to do just that.
The pancreas is home to many different cells with many different functions. Acinar cells produce enzymes that help us digest our food. Ductal cells transport those enzymes. Islet cells include the beta cells, which secrete the insulin that clears glucose out of the blood stream.
But while there are many different kinds of cells with different functions, they all start as a basic cell type – called a pancreatic progenitor cell. Then they differentiate – that is, they grow into the various special cells types (acinar cells, ductal cells, islet cells, etc.).
Dr. Bonner-Weir and her team have found that ductal cells – the ones that transport enzymes — have a particularly easy time remembering what it was like to be a progenitor cell. And, in fact, they can be nudged backwards into their progenitor cell state – and then stimulated to differentiate into insulin-producing beta cells.
“It just takes a step or two back from these differentiated duct cells to get back to something that is more like the embryonic duct cell, which is not quite as specialized but it still knows it’s in the pancreas,” says Dr. Bonner-Weir. “One of the things we’ve been doing through the years has been both looking at this process, and at what can stimulate the duct cells to replicate and then differentiate into beta cells.”
They first recognized the duct cells’ ability when studying the growth of new sections of the pancreas. When the pancreas grows in size (due to normal growth, or changes such as pregnancy or obesity), the duct cells replicate themselves to make up for the new increase in demand for their services.
“What we’ve been able to see is that whenever you make the duct cells replicate you end up getting new islet cells,” she says. They have been watching this process play out both in culture dishes and in rodent experiments.
She hopes that this discovery could lead to the development of a medication that could force ductal cells to turn into beta cells in the human body without having to grow new areas of the pancreas. But understanding this process could also help with research that is trying to create beta cells in a culture dish to be transplanted into patients. Some researchers are starting with stem cells and trying to develop them into insulin-secreting beta cells.
“Right now, I think at best, they get about 30 percent [beta cells out of the cells they start with],” she says. “Yet they get a lot of duct cells…so if we know how the duct cells get stimulated to actually become beta cells then that might be able to be overlaid onto those in vitro protocol.” This could allow researchers to get much higher beta cell yield for beta cell transplantation, bringing us closer to a cure.