The DRI’s Tissue Engineering group is aggressively pursuing the development of nanoencapsulation technology, the newest area in immunoisolation research.  The scientific team is applying the same layering technology that is currently used by the electronics, optics and sensor industries to surround the cells with a protective casing.    

By adapting this methodology to cell-based science, researchers are developing biocompatible coatings on the same scale as the cell membrane. These coatings can serve as a type of “camouflage” for the implanted islets, allowing them to go unnoticed by the body and avoid inflammatory reactions or immune attack.  

Another major advantage of this type of encapsulation is minimizing the size of the capsule and virtually eliminating the problem of oxygen delivery created by the space inside traditional microcapsules.  

The very thin coating has relatively little effect on diffusion in and out of the cell. Researchers are evaluating how effective multiple layers could be in protecting islets.   In another step forward, new technology is providing the tools to enable nanocapsules to actually defend themselves. DRI researchers are developing more “active” capsules by attaching anti-inflammatory molecules to their surface to reduce adverse reactions, such as the formation of clots and the infiltration of leukocytes into the islets.  

To further these efforts, the DRI established a partnership with Dr. Jeffrey Hubbell, professor and director of the Integrative Biosciences Institute, and professor of the Institute for Chemical Sciences and Engineering at Ecole Polytechnique Fèdèrale de Lausanne, Switzerland. Dr. Hubbell is world renowned for his work with biomaterials for tissue engineering and drug delivery.  

The collaboration will focus on developing new encapsulation devices and investigating strategies for local drug delivery at the transplant site.  

>> View Video Comments from DRI Researcher Cherie Stabler, Ph.D.

Ongoing evidence suggests that insulin-producing islets cells may have the ability to regenerate under certain conditions.  In fact, researchers have shown that islet regeneration can be induced in a variety of experimental settings, however pregnancy is the only normal state that results in natural development and growth of these cells.  

During pregnancy, the body accommodates the increased needs of the mother and the developing fetus by modifying a host of biological functions.  This includes a temporary expansion in the number of pancreatic beta cells required for regulating the blood sugar levels of both mother and baby.    Scientists at the DRI are now taking a closer look at this physiological phenomenon in order to determine methods to regenerate islets in people with type 1 diabetes.  

A critical first step in this process was to analyze the molecular signals that drive the natural islet expansion. Dr. Ricardo Pastori, director of molecular biology, and his team studied the role of a group of key molecules, called micro-RNA (miRNA), that control fundamental cell processes, such as the growth of islet cells.   

Micro-RNAs, which have unique properties and are master regulators of gene expression, have proven difficult to study due to their elusive nature. Until now, the methods that scientists have used to study miRNA have been unreliable.   In a major advance, the DRI team has been able to correctly measure and analyze miRNA expression, which is not only relevant in diabetes research, but is a significant finding for the entire medical research field.  

The study results were recently published in the journal Biochemical and Biophysical Research Communications, and the team presented their findings in March at a meeting hosted by the Cambridge Healthtech Institute in Boston.  

Dr. Pastori and his colleagues will now use this information to correctly profile islets isolated during pregnancy in rodent models to identify the novel genes and pathways involved in islet growth. These studies may lead to the development of novel methods to regenerate islets in the clinical setting. 

>>View Video Comments from DRI Researcher Luca Inverardi, M.D.    

Insulin-producing islet cells, which make up only one to two percent of the pancreas and are scattered throughout the organ, are surrounded by a network of connective tissue called the extra-cellular matrix (ECM). This dynamic complex of molecules is a key component of the islet micro- environment and affects the development, survival and regenerative potential of the cells. It also provides a natural cellular scaffold for supporting the islets and keeping them spatially distributed.  

During the islet isolation process, the ECM is broken down with the rest of the pancreatic tissue and the islets lose their natural “home.” This state, known as anoikis from the Greek word for “homelessness,” can also trigger cell death.  

DRI scientists are working to recreate the natural ECM environment by adding key proteins that are typically part of this tissue. The goal is to determine if there is a benefit in reconstructing an ECM that mimics the natural islet environment.  Researchers can then study the effects of housing the transplanted islets in their new home.  

>>View Video Comments from DRI Researcher Elizabeth Fenjves, Ph.D.