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Scientists tackle diabetes by reprogramming stem cells

Meri Firpo, Ph.D., will never forget the moment two years ago that shocked the international stem cell research community. A scientist revealed a novel process using genes to turn ordinary skin cells backward in development, returning them to pluripotent stem cells, the precursor cells capable of developing into any of the body’s cells.

Meri Firpo, Ph.D.

“No one knew whether to believe it,” she recalls. “It was too simple—and too outrageous.”

But Firpo recognized immediate potential for this powerful technique, which creates cells now known as induced pluripotent stem (iPS) cells.

Firpo, an assistant professor in the Stem Cell Institute and the Division of Endocrinology and Diabetes, has launched a promising cure-focused research tack using iPS cells to study type 1 diabetes. Using skin cells, she is creating iPS cells that have been reprogrammed to “forget” they once were skin. (Skin cells are abundant and easy to obtain. When their identity as skin is wiped away, they’re like blank slates.)

Then she’s prompting those iPS cells to develop into insulin-producing beta cells, the same pancreatic cells that are destroyed in people with type 1 diabetes.

The reprogrammed iPS cells represent an ideal model—” a human pancreas in a dish,” as Firpo explains—to learn more about individual causes of diabetes, such as whether a person’s islet cells somehow trigger a reaction from the immune system, or whether an errant immune system is at work. Such information ultimately may allow researchers to predict who’s likely to get diabetes and then prevent it.

Moreover, Firpo says, iPS cells could provide a unique opportunity to develop a patient-friendly treatment. Because they’d come directly from patients’ own bodies, iPS-generated beta cells may be easily transplantable back to those people, and —for some—might not require the extensive immunosuppressive drugs needed when cells come from another donor.

Down the hall from Firpo’s lab, Stem Cell Institute director Jonathan Slack, Ph.D., is taking a different approach to reprogrammed cells. But still, the two projects have overlapping methods that provide complementary information. ” They’re synergistic,” Slack says.

Slack is working to turn liver cells into beta cells. The liver is adjacent to the pancreas during an embryo’s development, he explains, and the two organs’ cells receive most—but not all—of the same developmental cues. Liver cells only need to be reprogrammed partway back before they can be steered toward becoming pancreas cells.

Already, Slack’s group has made insulinproducing cells that, unlike those derived from embryonic stem cells, can interpret glucose levels in the body and can release the insulin they produce in a timely manner.

“Our thinking has been greatly assisted by knowing about iPS cells and about Meri’s work,” Slack says. “When you’re in the same building and talking every day, it speeds things up a lot.”

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