Objective
The objective of this JDRF grant program is to demonstrate in a preclinical setting that a small-scale, densely-packed cell capsule with oxygenation keeps the islet transplant healthy through in vitro bench studies and a small animal trial. The study tests the newest implantable oxygen generator (smaller than the size of two dimes) and uses human islets. The small-scale system is designed to demonstrate that the insulin-secreting cells in the full-size capsule will be healthy and functional (glucose-responsive). That is, the system demonstrated here is scalable to the human-sized product. Future studies will utilize a large animal model to implant a full clinical system that would later be used in patients in clinical trials for FDA approval.
Background Rationale
Encapsulated cell transplantation with stem cells is a revolutionary approach being explored and developed by a number of academic and corporate laboratories. Many companies are working on the transformation of immature stem cells into fully functional insulin producing cells. Fewer, however, are at the stage where they are developing the full implant system. This “bioartificial pancreas” is an alternative to standard or intensive insulin injection treatment and an alternative to open-loop or emerging closed-loop insulin pump and implanted glucose monitor systems. It is intended to be more convenient for the patient as well as providing superior glucose control naturally through the biological action of cells. The encapsulated cell transplantation field for diabetes curative treatment has been greatly advanced by the development of stem-cell derived islets that can allow treatment of thousands of patients with a single cell lineage. Conventional unencapsulated islet transplantation (from donated organs) can only treat a very limited number of patients, and it requires life-long immunosuppression which is costly and leads to susceptibility to life-threatening infections.
The GLS approach to encapsulated cell transplantation is to provide the rate-limiting nutrient, oxygen, that is in short supply due to the immunoprotective membrane that protects the cells from rejection. The immunoprotective membrane is surrounded by a membrane that promotes local vascularization to aid in other nutrient transport and the glucose sensing and insulin secretion. The oxygenation approach has been shown in earlier experimental demonstrations and mathematical models to be the key to supporting the compact tissue to product sufficient basal and post-meal insulin. The GLS system will be a true bioartificial pancreas for the treatment of Type 1 Diabetes.
Description of Project
Giner Life Sciences, Inc. (GLS) is developing an oxygenated, implantable cell therapy capsule for the curative treatment of diabetes. A beta cell replacement solution will allow many Type 1 diabetes patients to live their healthiest lives free from the daily burden of managing the disease. People with diabetes will have the option of glucose control similar to that achieved by the normal human pancreas with a fully implanted system (all internal) that lasts several years. The patient will not be required to measure glucose via fingerprick nor inject insulin; the only maintenance will be recharging the device periodically via wireless charging (frequency to be determined: daily or every few days). It is envisioned that the patient can eat a normal, healthy diet like their normoglycemic friends and family. The capsule product, combined with beta cells from a partner firm, will go through clinical trials for an FDA approval as a biological and medical device product.
The unique GLS product features the supplemental oxygenation of densely-packed cell capsules to replace the oxygen that native islets receive through capillary blood vessels. The GLS solution provides immune protection and optimal viability and function to macroencapsulated, stem cell-derived islets. The solution is sized as a fully subcutaneous (under the skin) implant, requires no immunosuppressants, eliminates insulin injections, and provides patient-friendly, natural, biological regulation of glucose.
The miniaturized implantable electrochemical oxygen generator uses electrical power and water harvested from the body to produce oxygen to support densely packed tissue, and the surface of the implant is well-vascularized for biocompatibility and general nutrient and glucose/insulin exchange. The implanted battery is recharged periodically via (wireless) transcutaneous energy transfer, similar to charging a cell phone on a charging pad.
This proposed JDRF study focuses on the demonstration of the core GLS technology: the ability of the oxygen generator to support densely-packed tissue in the GLS custom oxygenation cell capsule. This study uses donor islet tissue.
GLS was launched in 2018 to commercialize its industrial parent company’s patented oxygenation technologies in life sciences applications. GLS has built an experienced team which has established strong active partnerships with medical device manufacturing firms, a preclinical animal testing facility, and cell biology and diabetes experts. GLS is currently seeking partners with stem-cell derived islets to complete the combination product development and move into clinical trials.
Anticipated Outcome
The short-term project outcome is a demonstration of two major components of the GLS technology: its oxygen generator and its cell capsule technology in preclinical models. The studies use special techniques to demonstrate that all the tissue in the cell capsule is healthy and functional (insulin secreting) and to demonstrate response rates to glucose that approximate what is seen in humans without diabetes. This demonstration is an inflection point to attract venture or strategic partner funding to move the technology to a full human implant system ready for large animal studies, clinical trials and an FDA approval. This demonstration builds on corporate-funded and grant-based work performed over the past several years.
The long-term project outcome is oxygenated, implantable cell therapy for the curative treatment of diabetes. A beta cell replacement solution will allow a high degree of freedom for many Type 1 diabetes patients to live their healthiest lives. The patient will have glucose control with a fully implanted system (no break in the skin after healing) that will last for several years. The patient will not be required to measure glucose via fingerprick nor inject insulin; the only maintenance will be recharging the device periodically (frequency to be determined: daily or every few days). It is envisioned that the patient can eat a normal, healthy diet like their nondiabetic friends and family. The whole product will go through clinical trials for an FDA approval as a biological and medical device product.
Relevance to T1D
The proposed technology is a key component of a curative treatment for Type 1 Diabetes (T1D) that replaces the natural function of the pancreas with a long-term implant of glucose responsive, insulin-producing stem cells. The full product, including the oxygen generator, is considered a “bioartificial pancreas” since the implant takes over the biological function of the pancreas cells destroyed by the T1D autoimmune disorder. As described above, the membrane-protected cells are lacking in oxygen due to the exclusion of blood vessels within the tissue implant. (The exclusion of blood vessels is necessary to protect the implant from rejection by the immune system.) The GLS solution is to provide oxygen through an implanted oxygenator that uses body water and an implanted rechargeable battery to produce oxygen through a chemical reaction. This patent-pending system allows a compact, fully implantable, low maintenance curative treatment.