mindblowingscience:

Did Scientists Just Develop A Viable Cure For Type 1 Diabetes?

In what’s being called one of the most important advances to date in the field, researchers at Harvard have used stem cells to create insulin-producing beta cells in large quantities. Human transplantation trials could only be a few years away.

Above: human-stem-cell derived beta cells. (Douglas Melton)

By using human embryonic stem cells, a research team led by Doug Melton created human insulin-producing beta cells that are virtually equivalent to normally functional beta cells in the kind of large quantities required for cell transplantation and pharmaceutical purposes.

Currently, the cell-derived beta cells are undergoing trials in animal models, including non-human primates.

The results have been published in the latest edition of Cell. In the study, Melton describes a step-by-step procedure that starts with stem cells and results in hundreds of millions of the vital pancreatic cells that secrete the hormone insulin, which keeps blood sugar levels in balance. It’s the lack of insulin produced by those cells — called beta cells — that’s the root cause of type 1 diabetes.

People with this condition often develop serious complications such as as heart disease, stroke, kidney failure, blindness, and premature death. To survive, people with Type 1 diabetes must have insulin delivered by injection or pump. Not to be confused with Type 2, it accounts for approximately 5% of all diagnosed cases of diabetes and affects about 3 million Americans.

Ultimately, these new lab-grown cells could be transplanted into diabetes patients, allowing them to create insulin naturally.

As Melton explains in Harvard Magazine, these cells, “read the amount of sugar in the blood, and then secrete just the right amount insulin in a way that is so exquisitely accurate that I don’t believe it will ever be reproduced by people injecting insulin or by a pump injecting that insulin.”

More from Harvard Magazine:

The cells share key traits and markers characteristic of beta cells with those from healthy individuals, including the packaging of the insulin they secrete in granules. In diabetic mice, they cure diabetes right away, in fewer than 10 days…

…But the how of creating beta cells from embryonic stem (ES) cells—directing the process of differentiation in either embryonic stem cells or induced pluripotent stem cells (derived from adult cells) to make any specific cell type, for that matter—has eluded scientists for more than a decade. Recapitulating the normal development program in a petri dish has proven extremely complicated, because a protein signal that has a certain effect at one stage of the process—guiding an ES cell to become, for example, one of the embryonic “germ layers” such as endoderm (from which the gut, liver, and pancreas develop)—might have an entirely different effect at a later stage, or in a higher concentration, or within a different environmental niche in the body.

The discovery reported today in Cell was thus not the result of serendipitous biological code-breaking, says Melton, but rather of “hard work.” “What we did to solve this problem is study all the genes that come on and go off during the normal development of a beta cell in mice and in frogs and in the human material that we could get access to. Once we knew which genes come on and go off, we then had to find a way to manipulate their activity…with inducing agents.” Melton and his team tested hundreds of combinations of small chemicals and growth factors before hitting on a six-step procedure in which two or three factors are added at each step, and in which the factor, its concentration, and the duration of its application all mattered.

The result was a scalable differentiation protocol that will be usable in industrial production of beta cells.

But as the Boston Globe reports:

Melton cautions that the work is still years from being tested in patients and many challenges, scientific and practical, remain. But he is gratified to have reached this point and even more motivated to continue, so as not to disappoint the millions of people who suffer from type 1 diabetes, which is usually diagnosed in children and young adults.

“We’re tired of curing mice,” Melton said in an interview. “Most patients are sick of hearing that something’s just around the corner; I’m sick of thinking things are just around the corner. But I do believe in the big picture.”

Melton hopes the cells could be ready to be tested in people in a few years. Already, cells are being transplanted into primates through a collaboration with a researcher in Chicago.

Melton’s work is expected to energize the diabetes research community.

It’s important to note that this discovery did not happen overnight. It arrived through the hard work of 50 graduate students and postdoctoral researchers who have worked on the project over the last 15 years.

Much more about this remarkable breakthrough at Harvard Magazine and The Boston Globe.

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