Periodic Reporting for period 2 - DELIVER (DELIVERy of advanced therapies for diabetes training network)
Reporting period: 2021-01-01 to 2022-12-31
The DELIVER programme is a training network based on DELIVERy of advanced therapies for diabetes. Advanced therapies are new medicinal products based on genes or cells and tissue engineering products (biomaterials), sometimes used in combination with medical devices. They herald revolutionary treatments for a number of chronic diseases affecting society, including the focus of the DELIVER programme, Diabetes Mellitus. As the incidence of insulin-dependent diabetes continues to rise around the world, so does the need for talented, innovative and entrepreneurial industrially-trained researchers. We aim to DELIVER the next cohort of translational research scientists in the field of advanced therapies and enabling medical devices for pancreatic islet transplantation, a cell therapy which is poised to become more widespread for the treatment of insulin-dependent diabetes.
Diabetes mellitus is a chronic disease characterised by high blood sugar due to problems with the hormone insulin. Insulin works to unlock all the cells of our body so that glucose from the food we eat can get inside and be converted into energy to power our muscles and organs. Diabetes affects 415 million people worldwide. There are two types of Diabetes- Type 1 Diabetes (T1D) and Type 2 Diabetes (T2D). T1D is an autoimmune disease and is not currently preventable. In TID, the body’s own immune system destroys the cells in the pancreas that produce insulin. Patients need to take insulin injections every day to survive as their body no longer produces insulin. Islet transplantation is a very promising therapy that has the potential advantage of re-establishing naturally-regulated insulin production. With this technique, pancreatic islets are harvested from donor pancreases and delivered to the liver by a catheter via the portal vein. There are however, many issues with this treatment; many islets are lost during and after transplantation due to lack of suitable support matrix, lack of an early oxygen supply and unfavourable inflammatory conditions. Furthermore, the patient must take lifelong immunosuppressive medications to prevent rejection, which have significant negative side effects, therefore islet transplant therapy is currently only approved for the most at risk “brittle” T1D patients. Therefore the main challenge for DELIVER is to improve insulin producing cell transplant therapy for T1D achieving sufficient delivery, retention and maintaining survival, engraftment and functioning of newly implanted islets. The objectives to overcome these challenges in DELIVER are 1) To develop technologies to overcome allo and auto rejection of transplanted pancreatic islets. 2)To provide newly intramuscularly transplanted islets with the nutritional supply that they need to survive as early as possible and 3) To develop biomaterial and medical device technologies for intramuscular islet transplantation. As a training programme the objectives also cover Researcher Training and Career Development, Communication, Dissemination and Exploitation and Management.
Diabetes mellitus is a chronic disease characterised by high blood sugar due to problems with the hormone insulin. Insulin works to unlock all the cells of our body so that glucose from the food we eat can get inside and be converted into energy to power our muscles and organs. Diabetes affects 415 million people worldwide. There are two types of Diabetes- Type 1 Diabetes (T1D) and Type 2 Diabetes (T2D). T1D is an autoimmune disease and is not currently preventable. In TID, the body’s own immune system destroys the cells in the pancreas that produce insulin. Patients need to take insulin injections every day to survive as their body no longer produces insulin. Islet transplantation is a very promising therapy that has the potential advantage of re-establishing naturally-regulated insulin production. With this technique, pancreatic islets are harvested from donor pancreases and delivered to the liver by a catheter via the portal vein. There are however, many issues with this treatment; many islets are lost during and after transplantation due to lack of suitable support matrix, lack of an early oxygen supply and unfavourable inflammatory conditions. Furthermore, the patient must take lifelong immunosuppressive medications to prevent rejection, which have significant negative side effects, therefore islet transplant therapy is currently only approved for the most at risk “brittle” T1D patients. Therefore the main challenge for DELIVER is to improve insulin producing cell transplant therapy for T1D achieving sufficient delivery, retention and maintaining survival, engraftment and functioning of newly implanted islets. The objectives to overcome these challenges in DELIVER are 1) To develop technologies to overcome allo and auto rejection of transplanted pancreatic islets. 2)To provide newly intramuscularly transplanted islets with the nutritional supply that they need to survive as early as possible and 3) To develop biomaterial and medical device technologies for intramuscular islet transplantation. As a training programme the objectives also cover Researcher Training and Career Development, Communication, Dissemination and Exploitation and Management.
The overall research aim of the DELIVER programme is to develop smart implanted devices to reverse diabetes, addressing current challenges with islet transplantation, engraftment and survival. DELIVER’s system aims to provide control for up to 5 years by increasing the longevity of the macroencapsulation devices and islet transplant.
In particular, the following points are the exploitable results obtained by all 6 DELIVER ESRs:
- DELIVER has developed an innovative immunoprotective strategy based on macroencapsulation devices and development of methods to overcome the Foreign Body Response (FBR).
- DELIVER has designed two separate drug delivery technologies, which will be incorporated into the medical devices and biomaterial implant to enhance islet oxygenation and vascularization.
- DELIVER has established oxygen diffusion testing chambers in order to test the oxygen diffusion coefficient of membranes. Moreover, insulin-producing-cell-containing pouches were developed. A real-time oxygen monitoring system was established for the pouches to measure the internal oxygen concentration.
- DELIVER’s application of Raman microspectroscopy, a non-destructive and marker-independent analytical technique, has provided detailed molecular information in regard to ECM characterization and immune cell identification. This finding can be expanded to further diagnostic applications.
- DELIVER’s aim was to develop a differentiation method to achieve greater differentiation efficiency to obtain a homogenous population of mature beta cells, with this aim; DELIVER ESRs are currently generating an inducible overexpression system of three markers of mature beta cells.
There have also been 9 papers published by DELIVER ESRs in peer reviewed journals.
In particular, the following points are the exploitable results obtained by all 6 DELIVER ESRs:
- DELIVER has developed an innovative immunoprotective strategy based on macroencapsulation devices and development of methods to overcome the Foreign Body Response (FBR).
- DELIVER has designed two separate drug delivery technologies, which will be incorporated into the medical devices and biomaterial implant to enhance islet oxygenation and vascularization.
- DELIVER has established oxygen diffusion testing chambers in order to test the oxygen diffusion coefficient of membranes. Moreover, insulin-producing-cell-containing pouches were developed. A real-time oxygen monitoring system was established for the pouches to measure the internal oxygen concentration.
- DELIVER’s application of Raman microspectroscopy, a non-destructive and marker-independent analytical technique, has provided detailed molecular information in regard to ECM characterization and immune cell identification. This finding can be expanded to further diagnostic applications.
- DELIVER’s aim was to develop a differentiation method to achieve greater differentiation efficiency to obtain a homogenous population of mature beta cells, with this aim; DELIVER ESRs are currently generating an inducible overexpression system of three markers of mature beta cells.
There have also been 9 papers published by DELIVER ESRs in peer reviewed journals.
DELIVER’s aim was to enhance the career perspectives and employability of researchers and contribution to their skills development. As the incidence of insulin-dependent diabetes continues to rise around the world, so does the need for talented, innovative and entrepreneurial industrially-trained researchers to translate advances in the field of pancreatic islet transplantation to the clinic. The DELIVER industrial doctorate training programme is built on the 7 principles of innovative doctoral training, as outlined by the European Commission. For a time, the unavoidable COVID19 situation had a massive impact in terms of access to research facilities, essential research items and plans for dissemination. However, the ESRs showed incredible resilience and dedication in the face of such adversity. This was an unforeseen risk, which has resulted in teaching the ESRs this resilience, dedication, strength of character and the ability to diversify to reach their goals. In terms of the impact on Type 1 Diabetes, DELIVER’s technology can potentially meet the end users’ expectation and wishes, offering a therapy that will improve the quality of life of individuals living with diabetes. Through, 1. Stimulation of angiogenesis, 2. Delivery of a macroencapsulation device, 3. Providing oxygen for the cells, 4. Monitoring and mitigating the foreign body response. The DELIVER device can be tested to deliver islets to replace those lost in T1DM and in turn control the condition in vivo. In the future this may yield a therapy that may remove the requirement for finger pricks and the constant monitoring of blood glucose as well as the subcutaneous administration of insulin. DELIVER is an example of how complementary collaboration between world-renowned experts and long-term dedication to basic research can have a potentially transformative effect on the entire field. DELIVER has shown the success that comes from working transparently and collaboratively together to lessen the burden of diabetes. This approach is more crucial now than ever before given that the pandemic has further multiplied the complications associated with diabetes. The technologies developed in the programme will be further translated by targeting additional research funding through HEU, particularly the European Innovation Council suite of programmes. We are currently targeting the Transition Challenge 2023 based on technology generated by DELIVER ESRs and this will further potentiate the impact of the DELIVER programme.