Periodic Reporting for period 4 - iNanoBIT (Integration of Nano- and Biotechnology for beta-cell and islet Transplantation)
Reporting period: 2022-04-01 to 2023-03-31
The iNanoBIT project aim was to apply nanotechnologies for imaging porcine pancreatic islet cellular transplants and human induced pluripotent stem cell-derived beta-cells and subsequent regenerative processes in vivo in small and large animal models.
Our focus is on diabetes, as one of the most challenging and economically important areas of medicine with very high level of importance for society. Specifically, we developed technological tool boxes to support the regenerative medicinal solutions for Type 1 diabetes (T1D), but we expect a much broader overall applicability for cellular/tissue imaging methods enabling follow up of various medical interventions for example osteochondral, hepatic, renal, lung, cardiac or brain cell therapy interventions. This imaging approach offer the potential for earlier detection of rejection or dysfunction of transplanted cells, tissues or organs, which would enable an earlier medical decision on switching to alternative therapeutic options for individual patients.
The project specific areas of development included:
1) novel highly sensitive nanotechnology-based imaging approaches allowing for monitoring of survival, engraftment, proliferation, function and whole-body distribution of the cellular transplants in a preclinical porcine model with excellent translational potential to humans;
2) development and validation of state-of-the-art imaging technologies facilitating the provision of new regenerative therapies to preclinical large animal models and patients;
3) overall contributing to the opening of a new market sector for
i) imaging equipment (SPECT, PET/MR, optoacoustic imaging) in preclinical large animal models and patients,
ii) nano-imaging molecule supplies allowing multimodality imaging of specific cell types with high sensitivity,
iii) validated transplantable in vitro differentiated human beta-cells and porcine xenotransplant islets thus reinforcing the European healthcare supply chain for regenerative medicinal products.
The iNanoBIT project toolbox elements paving the path towards a safe translation of regenerative medicinal cellular and tissue products, currently under preclinical and clinical trials, which is vital for the competitiveness of the European healthcare sector in this fast-growing area. The consortium of 5 SME and 3 Academic partners was coordinated and driven by the industrial partners from the field of nanotechnology, imaging and stem cell technologies, providing an ideal match and unique combination addressing the scope and expected impact of the call and arriving from TRL 3/4 starting points for the key technological elements to TRL6 levels of validated technologies ready for marketing.
Our focus is on diabetes, as one of the most challenging and economically important areas of medicine with very high level of importance for society. Specifically, we developed technological tool boxes to support the regenerative medicinal solutions for Type 1 diabetes (T1D), but we expect a much broader overall applicability for cellular/tissue imaging methods enabling follow up of various medical interventions for example osteochondral, hepatic, renal, lung, cardiac or brain cell therapy interventions. This imaging approach offer the potential for earlier detection of rejection or dysfunction of transplanted cells, tissues or organs, which would enable an earlier medical decision on switching to alternative therapeutic options for individual patients.
The project specific areas of development included:
1) novel highly sensitive nanotechnology-based imaging approaches allowing for monitoring of survival, engraftment, proliferation, function and whole-body distribution of the cellular transplants in a preclinical porcine model with excellent translational potential to humans;
2) development and validation of state-of-the-art imaging technologies facilitating the provision of new regenerative therapies to preclinical large animal models and patients;
3) overall contributing to the opening of a new market sector for
i) imaging equipment (SPECT, PET/MR, optoacoustic imaging) in preclinical large animal models and patients,
ii) nano-imaging molecule supplies allowing multimodality imaging of specific cell types with high sensitivity,
iii) validated transplantable in vitro differentiated human beta-cells and porcine xenotransplant islets thus reinforcing the European healthcare supply chain for regenerative medicinal products.
The iNanoBIT project toolbox elements paving the path towards a safe translation of regenerative medicinal cellular and tissue products, currently under preclinical and clinical trials, which is vital for the competitiveness of the European healthcare sector in this fast-growing area. The consortium of 5 SME and 3 Academic partners was coordinated and driven by the industrial partners from the field of nanotechnology, imaging and stem cell technologies, providing an ideal match and unique combination addressing the scope and expected impact of the call and arriving from TRL 3/4 starting points for the key technological elements to TRL6 levels of validated technologies ready for marketing.
The project made excellent progress in all aspects, by developing novel nanotechnology-based tools for monitoring beta-cell and islet cellular transplants which have been tested for their interaction with cells and medical devices ex-situ and after transplantation. New, highly sensitive imaging equipments for SPECT and optoacoustic imaging have been developed, improving the previous designs. Genetically modified infrared fluorescent reporter human pluripotent stem cell lines and pigs have been produced for better traceability of the transplanted cells and islets, respectively. A scalable 3D differentiation protocol of hiPSC-derived beta cells was developed to provide sufficient cell number for animal transplantation experiments. Genetically modified stem cells were successfully differentiated towards pancreatic progenitors and transplanted into mice and matured towards insulin-secreting beta cells. Rodent and large animal experiments have been successful to evaluate the imaging modalities.
Significant progress beyond the current state-of-the-art have been made in all aspects of biological and nanotechnological resources, imaging equipment and medical device development. The combination of such advances created novel medical options to treat type 1 diabetes by regenerative medicine approaches. If the foreseen preclinical and clinical trial processes are confirming the positive effects the clinical application of the technology would alleviate the burden of disease on society, especially due to diabetes-related medical complications, shortening the life-span and decreasing the quality of life of many.