Marc R. Garfinkel, MD

Our laboratory has two purposes.

First, as a clinical focus, we are participating in a human islet transplant trial. We are isolating and releasing purified human islets produced under cGMP conditions for clinical transplantation under an FDA-regulated clinical trial.

Second, the translational effort in the laboratory focuses on immunoisolation through microencapsulation. One of the important limitating factors in islet transplantation is the need for immunosuppression for islet survival. Our technique for generating islets encapsulated in polyethylene glycol (PEG), termed selective withdrawal, allows small, conformal coats around islets that allow normal functioning and inhibit the large molecules of the immune system from penetrating to the islet tissue.

Part I: Clinical Trial

We have undertaken a clinical trial to reproduce the results in the Edmonton trial of islet transplantation here at The University of Chicago. For this procedure, no surgery is needed. The islets from a deceased donor's pancreas are removed and injected into a major blood vessel of the patient's liver. The islet cells then begin making insulin. The transplant patient must take anti-rejection medicines, to prevent his/her immune system from attacking the new islet cells. However, islet transplants are still experimental. We still don't know what the long-term benefits and risks are. This is why the University of Chicago Hospitals is conducting a clinical trial on islet transplantation. We plan to give 10 patients islet transplants and follow them for five years to see how well they do. We hope our findings will provide information on the procedure's safety and success. Similar studies are being conducted around the world. Islet transplants performed at a Canadian research hospital over the last several years show promising results. In one group of 12 patients who received islet transplants, nine no longer needed daily insulin injections 10 months later. Our results show that, with eight subjects transplanted thus far, 3 are insulin independent, the longest at 19 mos from their final infusion of islets, 3 have some benefit (reduction of insulin requirement, improved glycemic control, avoidance of hypoglycemic episodes), and two have no function from their islet grafts. Additional trials with different means of producing the islets, different preservation techniques, and different anti rejection medications are planned.

Isolated human Islet in red islet team member in the cGMP lab

Part II: Basic Research

These success in clinical islet transplantation trials have increased the interest in transplantation of an endogenous insulin source. The major obstacles for the large scale application of this approach are the limited supply of donor tissue and the requirement of life-long immunosuppression use. One strategy for achieving immunosuppression-free tissue transplantation is the microencapsulation of islets. These encapsulation membranes ideally allow for free diffusion of nutrients, wastes, dissolved gasses, glucose, and insulin, while remaining impermeable to the components of the immune system, including complement proteins and immunoglobulins, compounds that have larger molecular weight.. We are investigating several semipermeable candidate membranes as the alginate-poly-L-lysine (PLL) and polyethylene glycol(PEG). We are also investigating the potential use of these microcapsules not just as passive stealth matrices but also as active carrier to insulin secretion by adding stimulatory peptides to their structures. These polymers are also being introduced around islets via alternative methods of droplet generation: the traditionally applied air-jacketed droplet generator, and a newer method termed selective withdrawal. Theoretically, microencapsulation of islets would provide a means of enabling immunosuppression free transplantation. In addition, given sufficiently complete immunoisolation, this technique raises the possibility of expanding donor tissue sources to animals. In addition, we are examining the effects of various peptides on blood vessel growth into and around encapsulated islets implanted in various sites, as well as the biocompatibility of various candidate polymers.

PLL capsules with Islets PEG capsules with Islets