New research uses an innovative technique to convert human stem cells into insulin-producing beta cells much more effectively. The insulin-producing cells created ‘rapidly cured’ type 1 diabetes in mice, and the benefits lasted for 9 months.
As many as 187,000 children and adolescents in the United States were living with type 1 diabetes in 2018.
An additional 1.4 million people aged over 20 years have the condition and manage it with insulin, according to the same statistics from the Centers for Disease Control and Prevention (CDC).
In type 1 diabetes, a faulty autoimmune response causes the immune system to attack and destroy insulin-producing beta cells within the pancreas.
Previous research has pointed to human pluripotent stem cells (hPSCs) as a potential therapeutic avenue for type 1 diabetes.
Pluripotent stem cells are an attractive option for researchers from a therapeutic standpoint because they can self-renew in lab cultures and can differentiate into a variety of cell types.
Researchers have previously used hPSCs to create insulin-producing beta cells. However, they were not able to do so effectively enough to cure type 1 diabetes.
Jeffrey R. Millman, Ph.D., an assistant professor of medicine and biomedical engineering at Washington University School of Medicine in St. Louis, is the principal investigator of the new study, which managed to overcome these previous obstacles.
He explains the challenges that halted the scientists’ progress until now. He says, “A common problem when you’re trying to transform a human stem cell into an insulin-producing beta cell — or a neuron or a heart cell — is that you also produce other cells that you don’t want.”
“In the case of beta cells, we might get other types of pancreas cells or liver cells.” While implanting these unnecessary — or “off-target” — cells does not cause any harm, Millman further explains that creating more of them offsets the number of therapeutically useful cells.
“The more off-target cells you get, the less therapeutically relevant cells you have,” he says.
“You need about a billion beta cells to cure a person of diabetes. But if a quarter of the cells you make are actually liver cells or other pancreas cells, instead of needing a billion cells, you’ll need 1.25 billion cells. It makes curing the disease 25% more difficult.”
However, the new research used an innovative technique that bypassed this problem. The findings appear in the journal Nature Biotechnology.
The new technique targets the cytoskeleton — or inner “scaffolding” — of the hPSC to direct their differentiation into pancreatic cells.
The cytoskeleton is a structure that helps cells keep their shape and offers the mechanical support that allows cells to move, divide, and multiply.
Targeting this structure allows the researchers to create fewer irrelevant cells and better functioning beta cells that helped control blood sugar.
Millman explains the novelty of the approach, saying, “It’s a completely different approach, fundamentally different in the way we go about it.”
“Previously, we would identify various proteins and factors and sprinkle them on the cells to see what would happen. As we have better understood the signals, we’ve been able to make that process less random.”
Millman and team transplanted “islet-sized aggregates” of beta cells differentiated from hPSC into mice with type 1 diabetes.
Pancreatic islets are groups of cells located in the pancreas. Some of these cells are insulin-producing beta cells.
This transplantation procedure “rapidly reversed severe preexisting diabetes in mice,” write the authors in their paper. The new stem cell protocol “can rapidly cure preexisting diabetes in mice,” they emphasize later on.
The reversal occurred at a rate similar to that of human islets, and normal blood sugar control was maintained for at least 9 months.
“We were able to make more beta cells, and those cells functioned better in the mice, some of which remained cured for more than a year.”
– Jeffrey Millman
The principal investigator continues to report on the highly significant findings.
“These mice had very severe diabetes with blood sugar readings of more than 500 milligrams per deciliter of blood (mg/dL)— levels that could be fatal for a person — and when we gave the mice the insulin-secreting cells, within 2 weeks their blood glucose levels had returned to normal and stayed that way for many months.”
However, the researcher also explains that there are a few more steps to follow before the research can help humans.
First, researchers must test the cells in larger animals and then find a way to automate the new technique to produce the billions of cells required for the millions of people that have type 1 diabetes.