Periodic Reporting for period 2 - DeLIVERY (Long-term Microphysiological Sample Imaging for Evaluation of Polypharmacy in Liver)
Période du rapport: 2023-05-01 au 2024-10-31
The project DeLIVERY – a project funded by the European Union’s European Innovation Council (EIC) Pathfinder Open programme – aims to build a radically new technology for personalized health care, which provides, for the first time, the possibility to investigate polypharmacy on individual patients.
Polypharmacy is the effect that the many combinations and permutations of drug mixtures which are typically prescribed to the chronically sick or the elderly population (e.g. painkillers, beta blockers, blood thinners, anti-depressants, and statins) have on the human body. Polypharmacy is becoming a major issue in the ageing population, as well over 10% of hospital admissions for people over 60 years of age are due to currently unknown interactions of the multiple drugs being prescribed by the specialized physicians and general practitioners routinely visited by the elderly. Currently, no single platform exists that can be utilized in a highly parallelized fashion to monitor such effects at the cellular and tissue level.
DeLIVERY will develop an integrated microphysiological system (MPS) culture and microscopic imaging platform specifically for the purpose of maintaining, treating and long-term imaging of patient-specific cells within their microenvironment. This MPS platform will allow physicians, biomedical scientists, and researchers to determine the individual response of human tissue biopsies to a combination of multiple drugs. DeLIVERY will enable individualized treatment options providing essential tools towards a better quality of life for older people by allowing improved personalized healthcare. Novel medicines with the potential to reverse the effects of ageing and non-alcoholic fatty liver disease (NAFLD) will be tested within typical polypharmacy contexts to determine possible interactions, and the DeLIVERY MPS system will be the main purpose-built platform to provide this service.
Polypharmacy is the effect that the many combinations and permutations of drug mixtures which are typically prescribed to the chronically sick or the elderly population (e.g. painkillers, beta blockers, blood thinners, anti-depressants, and statins) have on the human body. Polypharmacy is becoming a major issue in the ageing population, as well over 10% of hospital admissions for people over 60 years of age are due to currently unknown interactions of the multiple drugs being prescribed by the specialized physicians and general practitioners routinely visited by the elderly. Currently, no single platform exists that can be utilized in a highly parallelized fashion to monitor such effects at the cellular and tissue level.
DeLIVERY will develop an integrated microphysiological system (MPS) culture and microscopic imaging platform specifically for the purpose of maintaining, treating and long-term imaging of patient-specific cells within their microenvironment. This MPS platform will allow physicians, biomedical scientists, and researchers to determine the individual response of human tissue biopsies to a combination of multiple drugs. DeLIVERY will enable individualized treatment options providing essential tools towards a better quality of life for older people by allowing improved personalized healthcare. Novel medicines with the potential to reverse the effects of ageing and non-alcoholic fatty liver disease (NAFLD) will be tested within typical polypharmacy contexts to determine possible interactions, and the DeLIVERY MPS system will be the main purpose-built platform to provide this service.
The project started on May 1, 2022. The main work that was undertaken until May 1, 2023 is summarized, here:
- a prototype microphysiological systems (MPS) platform was devised, designed and produced. The prototype will be tested for its functionality jointly with partners at VUB, UniBi and UiT.
- prototype modular microscopes were devised, designed and produced. The prototypes are currently undergoing testing. Some prototypes will also be tested for their functionality jointly with partners at Cherry Biotech, EvkB, VUB, and UiT.
- precision cut liver slices have been tested for optimal long-term culturing conditions. Experiments are still ongoing and involve a number of different parameter.
- individual liver sinusoidal endothelial cells have been grown and treated with various drugs. Experiments are still ongoing and involve a number of different parameter.
- sections of human livers that were removed during surgical resection of various liver diseases have been collected after informed consent and will be used to optimize the imaging conditions of the prototype microscope systems and to validate image data obtained from live imaging experiments.
- materials transfer agreements for the exchange of the prototype systems have been prepared and are in the process of getting signed.
- a prototype microphysiological systems (MPS) platform was devised, designed and produced. The prototype will be tested for its functionality jointly with partners at VUB, UniBi and UiT.
- prototype modular microscopes were devised, designed and produced. The prototypes are currently undergoing testing. Some prototypes will also be tested for their functionality jointly with partners at Cherry Biotech, EvkB, VUB, and UiT.
- precision cut liver slices have been tested for optimal long-term culturing conditions. Experiments are still ongoing and involve a number of different parameter.
- individual liver sinusoidal endothelial cells have been grown and treated with various drugs. Experiments are still ongoing and involve a number of different parameter.
- sections of human livers that were removed during surgical resection of various liver diseases have been collected after informed consent and will be used to optimize the imaging conditions of the prototype microscope systems and to validate image data obtained from live imaging experiments.
- materials transfer agreements for the exchange of the prototype systems have been prepared and are in the process of getting signed.
A novel implementation of super-resolution structured illumination microscopy was developed, which is significantly improved with regard to its overall use of available laser power and which has a significantly improved field of view of up to 15x (150 µm x 150 µm vs. 40 µ x 40 µm) compared to current implementations of SR-SIM.
A new multi parametric microphysiological systems platform has been developed that will allow for the extended culture of liver cells and liver slices.
Novel drug analogues have been developed and tested that directly modulate the ultrastructural morphology of liver sinusoidal endothelial cells.
A new multi parametric microphysiological systems platform has been developed that will allow for the extended culture of liver cells and liver slices.
Novel drug analogues have been developed and tested that directly modulate the ultrastructural morphology of liver sinusoidal endothelial cells.