Periodic Reporting for period 2 - VANGUARD (New Generation Cell Therapy: Bioartificial Pancreas to Cure Type 1 Diabetes)
Période du rapport: 2021-01-01 au 2022-06-30
Type I diabetes is a global epidemic associated with a shortage of insulin-producing beta cells in the pancreas and is usually diagnosed in children and young adults. The current primary treatment for T1DM is exogenous insulin therapy, requiring multiple daily injections to control glucose levels. Poor glucose control leads to diabetes complications such as disease of the kidney, eyes and heart. During the last decades, important signs of progress have been made in clinical islet transplantation. However, islet transplantation relies on organ donors and requires lifelong immunosuppression to avoid the rejection of the transplanted islets. The process is also associated with a number of other complications and is currently only offered to a limited number of patients with severe forms of the disease.
VANGUARD aims to develop a cure for type 1 diabetes and thus make cell therapy a real and effective treatment available to a larger group of patients. The overarching objective of VANGUARD is to generate a novel breakthrough immune-protected bio-artificial pancreas that can be transplanted into non-immuno-suppressed patients. To achieve this VANGUARD will combine advanced tissue engineering platforms for 3D organoid generation, hydrogel design and bio-artificial organ assembly.
The project has the potential to drastically improve the success rate of clinical beta-cell replacement therapies, with exceptional advantages in terms of efficacy and patient safety. A bioartificial pancreas offers a breakthrough in the field of regenerative medicine and opens new horizons toward unlimited cell-based treatments for type 1 diabetes, thus overcoming the constraint of donor organ shortage.
VANGUARD aims to develop a cure for type 1 diabetes and thus make cell therapy a real and effective treatment available to a larger group of patients. The overarching objective of VANGUARD is to generate a novel breakthrough immune-protected bio-artificial pancreas that can be transplanted into non-immuno-suppressed patients. To achieve this VANGUARD will combine advanced tissue engineering platforms for 3D organoid generation, hydrogel design and bio-artificial organ assembly.
The project has the potential to drastically improve the success rate of clinical beta-cell replacement therapies, with exceptional advantages in terms of efficacy and patient safety. A bioartificial pancreas offers a breakthrough in the field of regenerative medicine and opens new horizons toward unlimited cell-based treatments for type 1 diabetes, thus overcoming the constraint of donor organ shortage.
The main results that have been achieved by the end of the second reporting period include the following points:
During the first year, additional batches of primary human amniotic epithelial cells (hAECs) have been isolated, characterized, and banked. The immunomodulatory and anti-inflammatory capacities of primary hAECs have been assessed in vitro and the results of this study have been published. The proof of concept of genome editing was also demonstrated.
The organoids generated by the consortium demonstrate significant improvement in glucose-stimulated insulin secretion and better vascularization after transplantation in the immune-deficient mice. The batches of hydrogels were generated, characterized, banked and distributed to the consortium for further studies. Performed studies show that gels favour cell function and viability in vitro. The protocols of bioartificial pancreas assembly were optimized and its single components were functionally tested. Finally, a systematic review of ethical considerations of using organoids in research and clinical care has been conducted and published.
To facilitate an interdisciplinary discussion on ethical aspects of bioartificial organs VANGUARD has organized an international online workshop. In order to make this discussion widely accessible, the meeting report and the video recording have been made available online via the VANGUARD project website and TransplantLive (the educational platform of ESOT).
During the first year, additional batches of primary human amniotic epithelial cells (hAECs) have been isolated, characterized, and banked. The immunomodulatory and anti-inflammatory capacities of primary hAECs have been assessed in vitro and the results of this study have been published. The proof of concept of genome editing was also demonstrated.
The organoids generated by the consortium demonstrate significant improvement in glucose-stimulated insulin secretion and better vascularization after transplantation in the immune-deficient mice. The batches of hydrogels were generated, characterized, banked and distributed to the consortium for further studies. Performed studies show that gels favour cell function and viability in vitro. The protocols of bioartificial pancreas assembly were optimized and its single components were functionally tested. Finally, a systematic review of ethical considerations of using organoids in research and clinical care has been conducted and published.
To facilitate an interdisciplinary discussion on ethical aspects of bioartificial organs VANGUARD has organized an international online workshop. In order to make this discussion widely accessible, the meeting report and the video recording have been made available online via the VANGUARD project website and TransplantLive (the educational platform of ESOT).
For the past 20 years, and despite all its limitations, the current state of the art in clinical cell therapy for type 1 diabetes has consisted of islet of Langerhans transplantation (i.e. transplantation of the unmodified insulin-secreting mini-organs enzymatically extracted from a donor pancreas). A few clinical attempts at transplanting ATMP have reached phase 1 level, but have failed to show any clinically relevant effect.
Ambitious projects have even started by combining a macroencapsulation device strategy with stem cell-derived beta cells or xenogeneic islets, without first going through an allogeneic stage. In contrast, VANGUARD will use a stepwise strategy, moving from allogeneic islet cell organoids to a more complex, but still allogeneic, bioartificial pancreas, constructed by “encapsulating” organoids into a biological scaffold.
The primary ambition of the VANGUARD consortium is to deliver a game-changing ATMP in the treatment of type 1 diabetes. The major deliverable of the project will represent a major breakthrough compared to islet of Langerhans transplantation, the only cell therapy for diabetes current in clinical practice. Breakthrough achievements are represented by increased potency/efficiency that will allow single-donor transplantation, immune protection that will dispense with the use of chronic systemic immunosuppression, and graft retrievability. Furthermore, VANGUARD strategy will dramatically reduce the long-term financial burden of the diabetic disease as well as the human consequences in terms of quality of life, permitting the large-scale treatment of diabetes at non-complicated stages through functional transplantation without the drawbacks of full immunosuppression.
Ambitious projects have even started by combining a macroencapsulation device strategy with stem cell-derived beta cells or xenogeneic islets, without first going through an allogeneic stage. In contrast, VANGUARD will use a stepwise strategy, moving from allogeneic islet cell organoids to a more complex, but still allogeneic, bioartificial pancreas, constructed by “encapsulating” organoids into a biological scaffold.
The primary ambition of the VANGUARD consortium is to deliver a game-changing ATMP in the treatment of type 1 diabetes. The major deliverable of the project will represent a major breakthrough compared to islet of Langerhans transplantation, the only cell therapy for diabetes current in clinical practice. Breakthrough achievements are represented by increased potency/efficiency that will allow single-donor transplantation, immune protection that will dispense with the use of chronic systemic immunosuppression, and graft retrievability. Furthermore, VANGUARD strategy will dramatically reduce the long-term financial burden of the diabetic disease as well as the human consequences in terms of quality of life, permitting the large-scale treatment of diabetes at non-complicated stages through functional transplantation without the drawbacks of full immunosuppression.