Surgeons Create Functional Artificial Pancreatic Tissue

Surgeons from Massachusetts General Hospital, Boston, are reporting on a whole new strategy for controlling insulin dependent diabetes without daily injections of insulin. The surgeons have bio-engineered a novel matrix that serves as a scaffold for seeding supportive stem cells as well as pancreatic islets (the cells that produce insulin in the pancreas).

In a proof-of-concept study presented at the 2010 Annual Clinical Congress of the American College of Surgeons, the researchers note that the matrix not only helps to understand the micro-architecture of the pancreas, but also prolongs the survival and preserves the function of the islets. Islets survived longer in the bio-artificial matrix than in conventional transplanta-tion sites, and they produced significantly more insulin when challenged with glucose. “Islet cell transplantation is the only treatment of insulin dependent diabetes that can consistently establish insulin independence. However, islets only feel at home in the pancreatic niche, and therefore their survival and ability to produce insulin declines rapidly if transplanted, for example, in the liver” according to Claudius Conrad, MD, PhD, primary investigator and chief resident in surgery at Massachusetts General Hospital.

“The pancreas provides a very special environment for islets,” he explained. “By default, the survival and function of the islet cells will always be worse in any organ other than the pancreas. To engineer an endocrine pancreas, islet- and stem cells require an extracellular matrix (ECM) that provides specific archi- tecture, microstructure, and most importantly microvasculature to form the islet cell specific niche,” he said.

Dr. Conrad and his colleagues are attempting to form a cellular structure that mimics the natural resting place on which the islets thrive. “We are trying to improve the survival and the functionality of the islets by creating their pancreas specific niche,” he explained.

The matrix was formed by removing cells from pancreatic tissue with biological deter-gents so only the proteins that hold the cells together were left. The resulting matrix was seeded with donor islet cells and supportive stem cells, and the entire construct was successfully trans-planted and maintained in a recipient animal model using microsurgical techniques.

Although the research is still at an early stage, Dr. Conrad believes a clinical trial of in patients with insulin dependent diabetes is likely in the near future. “The difficult aspects of the concept, such as decellularizing the pancreas by means of detergents, subsequent cellular seeding, and transplantation, have been worked out. I am very excited about the prospect of bioengineering an endocrine pancreas that could cure patients with insulin dependent diabetes. I think we are very close to the clinical application of this entirely novel concept,” he said.

Jeremy Song; Christian Schuetz, MD; Benjamin Clippinger, MS; Joseph P. Vacanti, MD, FACS; James F. Markmann, MD, PhD, FACS; and Harald C. Ott, MD, also participatedin the study.