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Progress Toward a Cure: Mimicking the Native Pancreas   

by Diabetes Research Institute on Thursday, May 12, 2011 at 11:03am on T1 Diabetes Cure - Global Headquarters and Diabetes Research Institute Facebook pages.

Hi Everyone! We thought we should give you an update on our work to improve cell replacement strategies.

First a little background: Since the first clinical islet transplants in 1984, researchers have used the liver as the preferred site to infuse healthy islets to restore natural insulin function. The site was selected for several reasons: The liver could be accessed without major surgery. Instead, a catheter or small tube could be inserted into a vein leading to the liver. The procedure could be performed in a radiology suite as an outpatient; The liver is a highly vascularized organ, which is critical for oxygen delivery to the insulin-producing cells.  Finally, not wanting to disturb the delicate pancreas, the liver offered an option based on the roles of the pancreas and liver in insulin production and glucose control.

In recent years, researchers have learned a lot about the adverse effects of anti-rejection drugs on the islets infused in the liver. While suppressing the immune system and blocking immune attack of the foreign islets, the drugs are toxic to organs and the islets themselves. Unfortunately, the islets are exposed to the highest levels of these drugs which are metabolized in the liver. In addition, islets infused flow to "pockets" in the organ and can "pile-up" or cluster together preventing some of the islets from getting adequate amounts of oxygen, causing cell death. This, along with inflammation, motivated researchers to explore alternative sites.

DRI researchers are exploring several ways to approach this. In one of the initiatives, we're using bio-engineering principles to create a more suitable environment for cell replacement.  Combining all of the expertise of our DRI scientists in tissue engineering, immunology, drug delivery, cell biology and surgery, we are developing a bio-artificial site that mimics the native pancreas.

To prevent islets from piling up or clumping in the liver, the team has created a sponge-like scaffold that creates "space" and separation of islets similar to the pancreas, allowing oxygen to reach all of the islets. The DRI team is also testing the addition of other cell types to be loaded into the scaffolds along with islets. These cells have shown the ability to decrease inflammation and promote blood vessel growth. The scaffold can also house oxygen promoters and other agents that can enhance cell function and long-term survival.

The loaded scaffold can be placed in a variety of sites. DRI is testing the creation of a "pouch" in the omentum - an apron-like tissue covering the abdomen. Collaborators are testing other sites including muscle, bone marrow and a subcutaneous site, meaning just under the skin.

We look forward to keeping you posted on this exciting work, especially as we move into clinical trials within the year.

 

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