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A technique that allows the insulin-producing cells that are destroyed by type 1 diabetes to be re-created in the lab could help researchers understand how the disease develops and perhaps lead to more effective treatments for the condition.

A study published today in the Proceedings of the National Academy of Sciences describes a way to create induced pluripotent stem (iPS) cells from ordinary adult cells taken from patients with type 1 diabetes. These stem cells then can be reprogrammed to produce all of the cell types relevant to the disease.

“What you get is the ability to watch, for the first time, type 1 diabetes develop,” says senior author Douglas Melton, a professor of natural sciences at Harvard University and co-director of the Harvard Stem Cell Institute. “Until you watch a disease develop, you will not understand the mechanism, and you therefore cannot devise any kind of sensible treatment or cure.”

Melton and his colleagues show that the reprogrammed iPS cells–so called for their ability to give rise to many cell types–can be spurred to differentiate into tissue resembling the insulin-producing pancreatic beta cells that are destroyed by the immune system in type 1 diabetes.

Embryonic stem (ES) cells have long been the gold standard for deriving pluripotent cell lines. But ES cells can only be used to create disease models for disorders such as cystic fibrosis, where the genetic underpinnings are straightforward. Because the genetics underlying type 1diabetes are complex and poorly understood, researchers have no way to identify diabetes-specific ES cells.

Therefore, iPS cells derived from patients known to be diabetic offer the best hope for modeling the disease by allowing researchers to generate diabetes-specific versions of all the relevant cell types: the pancreatic beta cells, the immune cells that destroy them, and the thymus cells that orchestrate their destruction.

By creating all these cell types from a single diabetic patient, it’s essentially possible to reconstruct the disease in a laboratory, says Jeanne Loring, founding director of the Center for Regenerative Medicine at the Scripps Research Institute in La Jolla, CA. “It’s completely mind boggling that you can actually study human disease in a dish,” says Loring, who was not involved in the new work.

This kind of model is especially important in type 1 diabetes, Loring adds, because while the disease is known to run in families, its genetic cause remain obscure. “By capturing the flawed cells and probing their dysfunction, researchers could begin to forge such an understanding.

Ultimately, Melton plans to construct a “living test tube” for probing the interplay between the beta cells and the immune system in diabetes. He hopes to use the diabetic iPS cells to generate all three relevant cell types and then to put those cells into a so-called humanized mouse that can accept human cells to see how they interact.

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Credit: PNAS

Tagged: Biomedicine, Diabetes, diseases, iPS cells, insulin, insulin-producing cells

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