Pancreatic islet transplantation is a surgical procedure used in the treatment of patients with type 1 (or latter-stage type 2) diabetes. It involves transplanting islets of Langerhans (hormone-producing pancreatic cell clusters) from a donor pancreas to the patient’s pancreas, with the goal of regulating blood glucose levels and minimizing hypoglycemia and diabetic complications. This groundbreaking procedure can provide near-physiologic results; unfortunately, it is not without its challenges, all of which have precluded it from becoming a reliable and widely adopted form of treatment. These challenges include:

A shortage of donors. Donor islets are not readily available at present, making the procedure difficult to perform on a larger scale - especially since multiple transfusions are often required to achieve and maintain blood glucose regulation.

Diminishment of allograft function over time. Collagenase digestion, which is part of the method used to isolate islets from a donor pancreas, causes damage to the layer of tissue surrounding those islets (the islet basement membrane, or islet-bm). This damage in turn leads to a loss of 50-70% of the islets immediately after transplantation, and a subsequent loss of allograft function. Studies aimed at restoring islet-bm integrity have thus far proved relatively unsuccessful.

The need for lifelong immunosuppression. Long-term immunosuppression therapy is required for patients receiving pancreatic islet transplantation. But these immunotherapeutics carry their own risks, including infection. Certain immunosuppressant drugs are also toxic to β-cells. 

Addressing the challenges

The team at StemBioSys hypothesizes that the development of an extracellular matrix-based (ECM) culture system to mimic the pancreatic niche will facilitate the procurement of larger quantities of allogenic islets - and that these islets will be high quality and less immunogenic than the islets sourced for current transplantation procedures. To test their hypothesis, StemBioSys has been awarded a $300,000 Small Business Innovation Research (SBIR) grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The main project aims are as follows:

1. To prepare a pl-ECM with human amniotic, iPSC-derived cells, using Good Manufacturing Practices (GMP), and to compare its architecture, properties and composition to pl-ECMs produced using pl-ECM research use only (RUO) procedures.

2. To study the human islets maintained on these pl-ECMs and determine their viability and function.
   

3. To evaluate the immunogenicity of these human islets, both in vitro and in vivo. Based on previous testing using rat specimens, the team observed attenuated immunogenicity on the ECM, which was attributable to the decontamination of “passenger” cells, and collagen restoration in the islet-bm.
   

4. To compare the viability and function of human iPSC-derived islets maintained on pl-ECM versus those maintained on fibronectin. 

This grant will enable StemBioSys to take important steps toward addressing the longstanding obstacles currently facing islet transportation, which in turn will open the door to more successful and readily available treatments for diabetes and other pancreatic conditions.

Located in San Antonio, TX, StemBioSys develops cell culture technologies licensed from The University of Texas Health Science Center, San Antonio. Our work represents the next evolution in stem cell research. For more information about StemBioSys and our patented technology, please contact us.