News & Research

    University of Illinois at Chicago, Chicago, Illinois

Microfluidic-based strategies for hypoxia preconditioning of microencapsulated human islets for transplantation

General Research Subject: Type 1 Diabetes

Focus: Immunology, Islet Biology, Islet Biology\Apoptosis, Transplantation

Type of Grant: Clinical Scientist Training Award

Project Start Date: July 1, 2012

Project End Date: June 30, 2015

Research Description

 Islet transplantation is a promising therapy for Type I Diabetes Mellitus (T1DM). However, current clinical trials have shown that an obstacle to widespread implementation is lack of islet for transplantation and long-term immunosuppression for graft maintenance.  Long-term immunosuppression has undesirable side effects for both patient and on transplanted islets; especially as immunosuppression damages islets over time. One promising strategy is the microencapsulation of islets, which would impede the immune system's attack on islets; thereby reducing or eliminating the need for immunosuppressive drugs. However, microencapsulation of islets has demonstrated a significant obstacle. In the body, islets have a high oxygen demand, which is met by a rich blood supply. However, microencapsulated islets do not have this blood supply, and rely on oxygen diffusion, the spontaneous movement of oxygen.  As a consequence, islets have insufficient oxygen to keep them alive in the long-term.

Recently, UIC has developed a microfluidic device, or "lab on a chip," that can mimic the constantly changing environment that islets live in including nutrients and oxygen levels. This device allows the measurement of factors that indicate how well islets are working including: intracellular calcium levels, mitochondrial function, and the secretion of insulin. In fact, UIC has developed an intermittent hypoxia (IH) protocol that has demonstrated an improve islet function under hypoxia for mice. In this proposal, we seek an understanding of functioning of microencapsulated human islets under normal conditions and stressed low oxygen conditions in order to develop strategies to improve microencapsulation as a clinical avenue.

Research Profile

Mentor: Jose Oberholzer, M.D.   Postdoctoral Fellow: Joshua Mendoza-Elias

What area of diabetes research does your project cover?  What role will this particular project play in preventing, treating and/or curing diabetes?

 Islet transplantation is a promising therapy for Type I Diabetes Mellitus (T1DM). However, current clinical trials have shown that an obstacle to widespread implementation is lack of islet availability for transplantation and long-term immunosuppression for graft maintenance. Long-term immunosuppression has undesirable side effects for both patient and on transplanted islets; especially as immunosuppression damages islets over time. One promising strategy is the microencapsulation of islets, which would impede the immune system’s attack on islets; thereby reducing or eliminating the need for immunosuppressive drugs. However, microencapsulation of islets has demonstrated a significant obstacle. In the body, islets have a high oxygen demand, which is met by a rich blood supply. However, microencapsulated islets do not have this blood supply, and rely on oxygen diffusion, the spontaneous movement of oxygen. As a consequence, islets have insufficient oxygen to keep them alive in the long-term; and when they die they cause inflammation, which causes the immune system to attack naked and microencapsulated islets.

Recently, UIC has developed a microfluidic device, or "lab on a chip," that can mimic the constantly changing environment that islets live-in including nutrients and oxygen levels. This device allows the measurement of factors that indicate how well islets are working including: intracellular calcium levels, mitochondrial function, and the secretion of insulin. In fact, UIC has developed an intermittent hypoxia (IH) protocol that has demonstrated an improve islet function under hypoxia in mice islets. In this proposal, we seek an understanding of functioning of microencapsulated human islets under normal conditions and stressed low oxygen conditions in order to develop strategies to improve microencapsulation as a clinical avenue.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

The Oberholzer lab at UIC,as well as other diabetes researchers around the world, are working towards the goal of making microencapsulated islets into functional cure and clinical avenue for patients with T1DM; and hopefully T2DM in the future. This project is aimed at learning more about how islets function when transplanted when naked and microencapsulated. Our goal is to improve islet function in microencapsulated islets so that perhaps in the future patients with T1DM and maybe even T2DM,can receive an islet transplant without the need for immunosuppression. In short, we hope that physicians in the future will not merely help slow the deterioration of your health and quality of life, but that we will truly be able to improve it.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?

In this country, there are an estimated 26 million people diabetics and an estimated 79 million prediabetics. According to the World Health Organization (WHO), this trend is also reflective in the number of diabetics which is expected to increase from 171 million in 2000 to 366 million by 2030. In short, the rate of diabetes is increasing at epidemic proportions. These people, who are dependent on insulin and other drugs, are faced with a diminished quality of life and health; and as a society we will all feel this loss unless we act to prevent it. In my lab and collaborating laboratories, we are pursuing many avenues to address this problem by investigating islet cell proliferation, microencapsulation, and microfluidics – in order to find a cure that we need for our future.

Professionally, I have been involved as a transplant surgeon for the past 15 years of experience in islet and pancreas transplantation. In addition to heading the islet transplantation program at UIC as chief or transplant, I am also involved as Scientific Director of the Chicago Diabetes Project; as a fundraiser running in the Chicago Marathon for the Cellmates On The Run; and lastly, as a community doctor conducting health screenings in Chicago’s underserved South Side communities such as the Perspectives Chart School Calumet Campus. I am personally involved with diabetes research whether it be at the bench, bedside, or community.

Specifically, this award will enable me to train and mentor my student, Joshua E. Mendoza-Elias, in applied microfluidics and microencapsulation as we investigate how improve islet function for applications in pancreatic islet transplantation. After completing a B.S. in Biology at Duke University, in 2009, Joshua joined the bioengineering program at UIC and began his medical school training in 2011. I believe that training awards such as these are important in helping to train and educate the next generation of physician scientist that will transform our feasible ideas into practical realities.

In what direction do you see the future of diabetes research going?

My laboratory and collaborators, have always maintained that our top priority is to develop a functional cure for T1DM by pooling are expertise and resources in islet cell proliferation, microencapsulation, and microfluidics. To this end, will continue to capitalize on this goal through cooperation by pooling our resources, expertise, and talent. With this award, we will be able to develop new technologies to understand islet physiology in the transplant setting.