Grants awarded to 17 projects for 2023

A total of 4,85 million SEK has been awarded in grants from the Swedish Fund for Research without Animal Experiments for 2023, divided between 17 projects.
The information about the projects are the researchers own descriptions from the applications for funding.

Tomas Bergström, Gothenburg University, 250 000 SEK 
Project:  Development of antiviral drugs against respiratory viruses without animal experiments
More information: Respiratory viruses such as Respiratory Syncytial virus (RSV) and Coronaviruses (CoV) such as COVID-19 are imminent threats to global health. No effective antiviral treatment exist to these both virus groups. We have discovered novel antiviral targets for RSV in form of EGF receptors (unpublished), and interactions between the non-structural protein 6 (nsp6) and Sigma-like receptors for CoV (Lundin A et al., PLoS Pathogens 2014;10(5):e1004166 and unpublished). Furthermore, we have characterized a novel herbal extract traditionally used in Tanzania (Mollel et al., J Ethnopharmacol. 2022; 292:115204).

We intend to develop these lead compounds to antiviral drugs. To this end, we have established air-liquid interface respiratory cell cultures of human origin for antiviral testing. This model builds a multi-layered cellular structure resembling the human airway epithelium, with retained ciliary function. These cells are grown with human growth factors and other defined chemical cell medium compounds, instead of calf serum and other animal products.

The object of the current project is to test the antiviral efficacy and cellular toxicity of our lead compounds against RSV and CoV in these ALI cultures. If these tests are successful, we intend to pursue clinical phase 1 trials in humans without animal experiments. The basis for this ambition is that no animal models are fully relevant for these two human viruses, which instead display their pathogenicity in the ALI model, which thus is better suited for evaluation. At our lab, we have BSL3 facilities in which experiments on COVID-19 are performed. experiments on RSV and other CoV are performed at BSL2 level. If successful, clinical application of the findings of the project could be fast, given the current pandemic situation.

Matteus Bruschettini, Cochran Sweden, 250 000 SEK
Project:  Outcome data differences amongst clinical and preclinical studies in neonatology
More information: This research project aims to assess outcome data differences amongst clinical and preclinical studies within two clinically relevant topics in neonatology, i.e. the administration of caffeine and opioids to preterm infants. Moreover, an exploratory analysis on the effect of sex will be conducted.

This application includes three research projects:
1. To assess the benefits and harms of caffeine administration in newborns a. in preterm infants (Cochrane review). Timeplan: January – May 2023 b. in newborn animal pups (systematic review of animal studies). Timeplan: January – May 2023
2. To assess the benefits and harms of opioids for sedation and pain management a. in preterm infants (Cochrane review). Timeplan: January – May 2023 b. in newborn animal pups (systematic review of animal studies). Timeplan: August – December 2023
3. To explore sex differences in the effects of caffeine and opioids a. amongst the animal studies (within project 1b; project 2b). Timeplan: 2024 b. implications on the clinical practice and research.

The findings of these research projects will allow to increase the methodological quality and guidance for authors of this type of studies and might be adapted to any field of medicine, beyond neonatology. Owing to the nature of the studies, there is no need to buy equipment for running the experiments. No ethical permits are required. Access to specialized tools to conduct screening and analysis of the data is provided by Cochrane, e.g. Screen4Me (artificial intelligence to screen thousands of studies), Covidence (online screening and data extraction), and RevMan (Cochrane’s main software).

The research team has longstanding experience in publishing systematic reviews and the concomitant analysis of preclinical and clinical studies. The main applicant has registered a Cochrane review on caffeine and opioids. The co-applicant Merel Ritskes-Hoitinga is the founder / current coordinator of SYRCLE (info on SYRCLE, see below).

Anna Erlandsson, Uppsala University, 350 000 SEK per year 2023, 2024, 2025
Project:  Investigating the role of astrocytes in Alzheimer’s disease, using human cell culture models
More information: Alzheimer’s disease (AD) is the leading cause of dementia. Yet, no treatments that limit neurodegeneration or slow down the disease progression are available. Hence, innovative therapeutic approaches are clearly required.

The key neuropathological hallmarks of AD are extracellular plaques, mainly consisting of aggregated Aβ, intracellular neurofibrillary tangles, composed of hyperphosphorylated tau and chronic inflammation. Decades of research have focused on neuronal abnormalities during AD progression, while glial cells, including astrocytes, have been given much less attention.

The aim of this project is to clarify the involvement of astrocytes in AD and to investigate their therapeutic potential by using advanced human cell culture models. Our previous results demonstrate that astrocytes engulf large amounts of aggregated amyloid-beta and tau, but then store, rather than degrade the ingested material. This incomplete degradation results in severe cellular stress and the release of extracellular vesicles containing neurotoxic content, which could be of relevance for AD progression.

To further investigate the impact of astrocytes in amyloid-beta and tau pathology, we will use cell culture models that mimic the central disease processes in the human AD brain. For this purpose, we will develop different co-cultures, close-cultures and 3D organoids of human iPSC-derived astrocytes, neurons and other relevant cell types. The cell models will be used to:
• Examine the role of astrocytes AD progression by spreading of pathological protein aggregates.
• Elucidate if antigen presenting astrocytes are driving the chronic inflammation in AD.
• Identify ways to reduce astrocyte-mediated neurotoxicity and disease spreading.
Being the most numerous glial cell type in the brain, astrocytes constitute a compelling treatment target. Our results will contribute with important data and hopefully pave the way for novel therapeutic strategies to halt AD progression.

Anna Falk, Karolinska Institute, 350 000 SEK per year 2023, 2024, 2025
Project:  Organoids as hosts and semi-in-vivo models of the human brain to reduce and replace animals
More information: The main objective of this 3R program is to develop human organoid systems that will act as hosts and “in-vivo-like” brains for transplanting cells to replace the use of animals.

There are two main reasons to develop brain organoid systems that mimics the human brain, one being that animal brains have been shown to be different to humans and thus sub-optimal for studies of brain disorders, second now with emerging stem cell technologies we have the chance and the responsibility to develop human “in-vivo-like” brain models for research and thereby replace animals.

We in my group are stem cell biologists with long experience in reprogramming and stem cell models of the brain. Here we would like to use our knowledge to create organoid models of the human brain that will be used as a substitute for animal brains for transplantation of cells for cancer studies, disease modelling of neuronal maturation and for cell replacement therapy studies.

The three different types of transplantation schemes we would like to investigate and develop are the following (listed in the order of number of animals that can be replacement), organoids as hosts:
a) For transplantation of tumour cells for studies of brain cancer
b) For transplantation of patient derived neural cells to investigate differentiation, migration, integration, maturation into a healthy “brain-like” environment
c) For studies on neural cells replacement in for example organoid models of Parkinson’s disease and Stroke

We have previously standardised stem cell culture and neuronal differentiation using defined, serum free and xenofree reagents, which creates robust stem cells showing close to none variability. Here we will develop the brain organoid system by replacing Matrigel with the defined and animal free 3D material BioSilk. The produced organoids will be investigated for their ability to host cell transplantation and thereby replace animal brains.

Marianne Jansson, Lund University, 300 000 SEK per year 2022, 2023, 2024
Project:  Animal-free lymphoid infection; clues to why HIV-2 is less aggressive and blunts HIV-1?
More information: The HIV-1 epidemic is still spreading. Thus, the need for a vaccine or cure is urgent. To identify virus-host mechanisms that could be targeted for cure strategies a fraction of HIV-1 infected individuals with spontaneous virus control, elite controllers, have been studied.

However, only 0.15% of HIV-1 infected individuals are elite controllers. In contrast, elite controllers among those infected with HIV-2, a benign form of HIV, has been estimated to 37%. Therefore, HIV-2 infection may represent a better model for finding cure strategies. In an epidemic study we showed that HIV-2 also delays HIV-1 AIDS development with 90% in HIV-1/HIV-2 dually infected. Furthermore, the blunting effect that HIV-2 has on HIV-1 progression was observed to be an early HIV-1 infection event.

We now want to identify mechanisms behind HIV-1 and HIV-2 differences, and how HIV-2 suppresses HIV-1. Since HIV primarily replicates in lymphoid tissue, infection experiments using blood-derived lymphoid cells do not provide a clinically relevant model. Humanized mouse and non-human primate models are therefore increasingly used to study early infection events taking place in lymphoid tissue.

To avoid use of animal models, we here aim to establish a novel model where infection of lymphoid tissue, from human tonsils, is used to dissect early events of HIV-1, HIV-2 and dual infections. The tonsil tissue will be infected with HIV-1 and HIV-2, individually and dually, and gene specific chimeric viruses will be constructed for deciphering virus-specific determinants of replicative capacity and host interactions.

The replication of the viruses, as well as the expression of genes and proteins in different cell populations, infected and bystander, will be analyzed using advanced bioinformatics including network analysis and modeling. By this we hope to contribute to the development of animal free infection models and strategies to prevent AIDS development in HIV-1 infection.

Per Malmberg, Chalmers Technical University, 150 000 SEK
Project:  Chemical imaging for skin permeation studies – an analytical approach to replace animal experiments
More information: We have recently shown that our animal-free skin permeation analysis approach can be used to study uptake of active pharmaceutical compounds (APIs) as well as to study metal uptake in skin for sensitization studies.

In this project we want to validate our method and compare to an existing skin model, NativeSkin and put this in contrast to the OECD approved artificial skin model, EpiDerm.

The aim for the project is to establish the model so that it can replace or significantly reduce existing in-vivo models and improve on already established in-vitro models. This by offering a more sensitive and flexible analytical approach that can replace and/or complement existing methods in the OECD guidelines for skin adsorption (no 427, no 428 and no 429) and measure metals and APIs simultaneously in the skin while being able to also trace endogenous effects in cells.

Ivan Nalvarte, Karolinska Institute, 275 000 SEK
Project:  A new model to study Alzheimer’s disease in human mini-brains
More information: Due to the lack of relevant and reliable in vitro models of Alzheimer’s disease (AD), the research field has been extensively based on animal models. Lately, the human disease relevance of animal models has been questioned, warranting the development of alternative models of AD. However, to establish a new relevant in vitro model of AD that can replace animal experimentation it is necessary to mimic AD progression in an immunocompetent and user-friendly setting. Such in vitro model is missing today.

Aim: The hallmarks of AD include cortical and hippocampal deposition of amyloid plaques, neurofibrillary tangles, and activation of local immune response that all contribute to extensive neuronal death and cognitive decline. The proposed project aims at developing an immunocompetent in vitro model of AD that recapitulates human pathology better than animal models, and that can be used in semi high-throughput.

Approach: The project will establish forebrain organoids from induced human pluripotent stem cells, uniformly grown in tailored simple-to-use semi-high-throughput bioreactors. We will explore AD induction by the use of Aftin-5 chemical that recapitulates sporadic AD. This is very interesting since sporadic AD is the most common form, but lacks adequate experimental models.

To address the impact of immune response on AD pathogenesis, we will establish co-cultures of forebrain organoids with isogenic microglia. This model will be validated against human AD brain samples. In this way, we aim at providing a more human relevant model of AD than current animal models, thereby replacing and reducing animal use in AD research.

Preliminary Results: We have successfully established human iPSCs in xeno-free conditions and derived both forebrain organoids and microglia from these. Preliminary data suggest successful induction of amyloid deposition upon Aftin-5 treatment. We are currently optimizing this induction and the microglia co-culture protocol.

Niloofar Nikaein, Örebro University, 300 000 SEK
Project: Systems biology of sepsis induced immunosuppression
More information: WHO reports that sepsis accounted for 20% of all global deaths in 2017. We need to understand the mechanisms behind sepsis in order to reduce its threat to global health. Sepsis involves a hyperinflammatory phase followed by suppression of the immune system i.e. immunosuppression.

The immune response to sepsis is typically investigated using animal models. The “Cecal Ligation and Puncture (CLP)” is the most widely used sepsis animal model in which animal intestine is punctured to let fecal material into the peritoneal cavity. Even if the animal is anesthetized during the experiment, we need to reflect on the potential suffering of the experimental animals which are also killed after the experiment.

We propose to build a computer model of sepsis-induced immunosuppression, without using animals, to reduce and replace animal models. The computer model is based on Ordinary Differential Equations (ODEs) and focuses on several central mediators of human immune system (TNF, IL1beta, IL-10, IL-1Ra and IL-18). We will employ ODEs to describe core reactions in related molecular pathways using reaction rates as unknown parameters. The goal is to estimate these parameters in a way that the model reproduces identical responses to real-life experimental data.

Our experimental data will be generated from a primary human monocyte cell culture model responding to consecutive endotoxin triggers. This protocol mimics monocyte reprogramming in immunosuppressed septic patients. The validated model will help develop and test new hypothesis and, design and optimize new animal-free experiments. This project is part of the research consortium X-HiDE [1], based at Örebro university which in collaboration with both academic and industrial partners, aims to explore core mechanisms of inflammation. Mathematical and biomedical teams within X-HiDE will engage in this project in close collaboration. More information: www.oru.se/english/strategic-initiatives/strategic-research-profiles/x-hide/

Mats Nilsson, Stockholms Universitet, 300 000 SEK per year 2022, 2023, 2024
Project:  The Design of a Glioblastoma Organoid-on-a-Chip for Drug Testing
More information: Glioblastoma multiforme (GBM), in addition to being the most common type of malignant primary brain tumor, is one of the tumors that has seen the least improvement in treatment options in the last half-century. The existing tools we have (mouse models, cell culture models) for testing efficacy are insufficient and inefficient.

New tools are needed. Specifically, a tool that tests a drugs ability to pass the BBB and reach the tumor, that recapitulates the GBM tumoral environment and complexity, while allowing efficacy to be assessed in the context of biomarkers. Toward that end, the project proposal is to develop an in vitro glioblastoma organoid on-a-chip that can be integrated into the drug discovery systems of tomorrow, and used to assess preclinical effectiveness of drugs on glioblastomas.

Elin Nyman, Linköping University, 350 000 SEK per year 2023, 2024, 2025
Project:  Computer models within inflammation that reduce the need of animal experiments
More information: The process of inflammation is important to understand since it is a key component in many common diseases: cancer, cardiovascular diseases, and infectious diseases such as covid-19 to mention a few. Even though substantial efforts have been made, there is a lack of a mechanistic understanding of both shared hallmarks of inflammatory processes, and mechanistic differences of importance for common diseases.

To study mechanisms, computer models has shown potential since they allow for quantitative hypothesis testing of proposed mechanisms. Developed models can be simulated to predict the outcome for new experiments and therefore used in knowledge-based experimental design. Such simulations can be extended to the scale of a whole population, where individual differences are included and therefore can be used to evaluate the effects of new drugs for different groups of individuals. Computer models can therefore bridge between detailed in vitro data and clinical observations – without the use of animal experiments.

In a collaboration between researchers at Örebro University, Linköping University, and AstraZeneca, the aim is to set up such a knowledge driven workflow to study the process of inflammation. We aim to extract and build functional general models of the process of inflammation, i.e. models that would be shared among both different organs and tissues and potentially also shared between different diseases. These general models can then be specialized in different ways to answer different clinically relevant questions about inflammation. In summary, this project will use computer models together with human-derived in vitro and clinical data from the inflammatory process. The models will serve as a basis for a knowledge driven workflow, where mechanistic knowledge can be connected to clinical outcome, and where the use of animal experiments become superfluous.

Penny Nymark, Karolinska Institute, 250 000 SEK
Project:  Toward risk assessment without animals: Development of Adverse Outcome Pathways for lung cancer
More information: The risk agents such as nanomaterials to cause cancer is complex to assess and currently based mainly on animal experimentation, even though non-animal alternative methods exist. Some of these cell-based methods and assays are accepted by regulatory instances for risk assessment, however, are mainly applied as weight of evidence information in addition to currently required animal data. Furthermore, novel high-throughput systems, capable of handling increasing numbers of samples in short time frames, require validation towards regulatory acceptance.

The new Adverse Outcome Pathway (AOP) concept is expected to simplify and improve the integration of alternative methods towards becoming gold standard regulatory accepted methods for risk assessment. AOPs describe toxic mechanisms causally connected to human organ injury and disease. They provide a basis for development of mechanism-focused alternative methods predictive of the risk for toxicity.

This project will continue to develop and refine an AOP for lung cancer, which has been developed with funding from Forska utan Djurförsök. The project will apply toxicological and data management expertise with the aim to integrate big data with high quality derived from a wide number of diverse nanomaterials, as well as to support efficient reuse of the project results. Novel data handling and integrative approaches will be applied in line with the recently established FAIR principles, which guide scientific approaches in order to make results Findable, Accessible, Interoperable and Reusable. Implementation of FAIR principles effectively supports efficient reuse and application of results in practical settings.

The overall aim of the project is to develop, facilitate and support the integration of AOP-aligned animal-free methods for cancer risk assessment of inhalable nanomaterials.

Ausra Perciulyte, RISE Research Institutes of Sweden, 325 000 SEK
Project: Validation in vitro method to replace the use of animals in studies of endocrine disruptors
More information: The aim of the study is to validate a method for its scientific robustness, maturity and ability to bridge existing gaps in endocrine disruptors characterization, replacing animal experiments with in vitro methods. More specifically the study aims at validating the method for the profiling of the steroid metabolome of human adrenocarcinoma commercially available cell line (H295R) by applying a liquid chromatography tandem spectrometry (LC-MS/MS), which separates and measures 19 precursors, intermediates and end-products of steroidogenesis after exposure to different concentrations of forskolin, an activator of steroidogenic pathways. The toxicological endpoints of the test are the levels of steroidogenesis metabolites.

No live animals are needed, since this is an in vitro method using a human cell line.

This method is an extension of the OECD TG 456 which covers steroidogenesis pathway in H295R cells. However, the assay is validated only for two hormones (estradiol and testosterone). This assay could allow a more detailed overview of the steroidogenic pathways and could be considered as an enhancement of OECD TG 456 since it has the potential to implement other models that assess the intracellular and extracellular concentrations of the various steroids and apply more advanced kinetics.

The advantages of this method, developed earlier (Ahmed et al., (2018)) compared to immunoassays that measure steroid levels, are the high throughput, the higher accuracy for low concentrations of steroids, the ability to distinguish between highly similar structures and the lower interference by other biomolecules. Impairment of steroidogenesis may lead to reproductive failure, and decreased learning and memory capacity in the population. Information regarding the steroid levels and the steroidogenic pathways, as well as the way they are affected by chemical compounds allows for better policy making and protection of the public, and informed decisions on chemical selection.

Nicolas Pillon, Karolinska Institute, 300 000 SEK
Project:  In silico comparative profiling of skeletal muscle immunometabolic responses
More information: The rapid advancement in technology has allowed wide-scale use of ‘omics’ in human and many model organisms, but the amount of biological data generated surpasses the ability of researchers to comprehensively process it. We here propose to add “reuse” as a fourth “R” to the 3R principles of animal experimentation. The overarching aim of this project is to promote the reutilization of data with the objective to reduce the need for preliminary exploratory analyses in animal models.

We will use in silico analyses to decipher subtypes of immunometabolic responses in skeletal muscle to define novel interventional strategies that extinguish or promote selective components of inflammation to improve metabolism.

This project will develop innovative bioinformatic approaches taking advantage of publicly available data to identify novel therapeutic targets and generate accessible omics databases of human and mouse. The cross-species comparison of the response of skeletal muscle will provide a complete map of the mouse and human responses to exercise and metabolic diseases and therefore help increase translatability of exercise and metabolic research.

Alexandra Stubelius, Chalmers University of Technology, 225 SEK
Project:  An in vitro platform to evaluate nanomedicine performance in blood
More information: Engineered Nanoparticles (NPs) are emerging as promising drug carriers in many medical applications, but current knowledge gaps with regards to how the biological environment shape NP performance limits broad clinical translation. The translation has in part been hampered by suboptimal research practices that propagate biases and hinder reproducibility. In particular, the field struggles with issues regarding the use of uncharacterized or poorly characterized materials, poor understanding of the relevant biology and mechanisms, large between-model heterogeneities, and wrongful model and study designs.

Most NPs need to be administered via intravenous (i.v.) injection and subsequent transport in the blood, where interactions with serum proteins, immune cells and vasculature walls can diminish their efficacy and dose. Moreover, NPs need to effectively exit the blood vessels at the target organ and be retained in tissue; this requires them to traverse endothelial cell and extracellular matrix (ECM) barriers.

The field still struggles to recapitulate human outcomes in animal experiments, as the in vivo settings does not provide sufficient molecular information to rationally design improved NPs, and the use of large numbers of test animals in NP screens is ethically questionable. Therefore, we propose here a novel approach to model NP transport in blood, relying on the development of blood vessel mimetic microfluidic devices lined with human endothelial cells and filled with media that recapitulate key features of human blood. This model system will allow NP performance to be assayed with the high precision that is needed to understand their biological function, paving way for rational design of improved nanocarriers and opening new avenues for the development of personalized precision medicines.

Jane Synnergren, Skövde University, 300 000 SEK
Project:  Reduce the need for animal models by advanced 3D in vitro cardiac hypertrophy disease model
More information: Animal models have been required to increase our understanding of the pathogenesis and underlying causative mechanisms associated with cardiac hypertrophy (CHT). Rodent models have been used for decades as disease models for CHT, but do not fully recapitulate the human CHT pathophysiology. In recent years, human pluripotent stem cells-derived cardiomyocytes (hPSC-CMs) have emerged as a powerful tool to overcome the limitations of using animal models to study CHT. hPSC-CMs can be produced at high scale and purity for disease research and drug development. However, a major hurdle for their application is the immature state of the hPSC-CMs. Thus, more knowledge about the developmental drivers of hPSC-CM maturation is needed in order to implement strategies to enhance the maturation of hPSC-CMs.

Recent data show that advanced 3D culture methods using bioprinting, organoids, and multi-cell type culturing improve the maturation and functional properties of hPSC-CMs. This project will extend our work on 2D CHT disease models and use organoids to develop a more advanced 3D CHT disease model based on CMs of human origin. To induce CHT characteristics the model will be exposed to endothelin-1. The 3D disease model will provide novel means to explore the dynamic changes and remodeling that characterize CHT progression, and identify causative molecular mechanisms associated with cardiomyocyte maturation. Development of advanced CHT disease models would greatly benefit from the generation of fully mature hPSC-CM since it will allow a more accurate recapitulation of the CHT disease phenotype in an in vitro setting, replacing current animal models.

The project will also collect large-scale data from in vitro models and explore how digital models can be used to simulate key mechanistic for CHT progression, and investigate how concept of digital twins, digital organs and digital cells can reduce the need of animal models.

Erica Zeglio, Stockholm University, 225 000 SEK
Project: Electrophysiological tools for accessible, animal-free proarrhythmia safetyscreening
More information: Cardiovascular disease is the leading cause of death in the U.S. and Europe , leading to extensive efforts toward the cardiac safety assessment of new drug in the preclinical phase. However, to date most drug withdrawals are related to cardiac safety , half of them involving torsades de pointe (TdP, a type of abnormal heart rhythm that can lead to sudden cardiac death). Such outcomes point out the inadequacy of current preclinical models, which do not recapitulate all the relevant aspects of the human heart. Specifically, they fail to provide an accurate reproduction of the electrophysiological behavior of human cardiomyocytes , making them unreliable detectors of the proarrhythmic effects of drugs that can induce TdP.

Both public and private efforts have been taken to develop better preclinical models and assays to screen drugs for cardiotoxicity, most notably through the Comprehensive in Vitro Proarrhythmia Assay (CiPA) consortium. CiPA proposes the use of human stem cell-derived cardiomyocytes cultures and electrophysiological evaluation through multi-electrode arrays (MEAs) or voltage-sensing optical techniques (VSO). This approach has already shown to be effective in predicting drug-induced proarrhythmic effects.

However, the costs and throughput of this paradigm are still behind those of animal-based assays. In fact, recent studies still propose animal models as a viable, convenient, and cost-effective means to study drug-induced cardiotoxicity. The goal of this project is to develop an electrophysiological platform that will increase the throughput and reduce the costs of animal- and serum-free cardiotoxicity assays. We will use printed electronics to produce high throughput MEAs and apply them to monitor human cardiomyocytes derived from embryonic stem cells, demonstrating how high-fidelity toxicology screening can be made as accessible and convenient as the inferior animal-based studies.

Lena Öhman, Gothenburg University, 250 000 SEK
Project:  Human intestinal organoids as a tissue based model system for studying cellular mechanisms of intestines
More information: Many diseases of the gastrointestinal tract are multifactorial and there is not one single experimental animal model that resembles all aspects of human conditions, irrespective of disease. During recent years, the importance of the interaction between the host and the local intestinal microenvironment, thus the microbiota and metabolites they produce, for disease generation has become evident.

The aim of this project proposal is therefore to develop a tissue based model system making use of our in house developed intestinal organoids for determining epithelial events giving rise to intestinal diseases, alongside assessing cellular mechanisms of therapeutic drugs. Our unique model is based on organoids from healthy donors, which are stimulated with fecal supernatants containing luminal factors, from patients and healthy subjects, giving rise organoids with different characteristics, representing disease-like and healthy-like “mini-guts in a dish”. Thus, our hypothesis, supported by preliminary data, is that organoids cultured in the presence of fecal supernatants reproduce the intestinal conditions of the donors who provided the fecal material. The effects of fecal supernatants on organoids are determined by microscopy, RNA and protein profiles. This organoid system will allow us to determine events of the epithelium perpetuating disease as well as mechanisms of therapeutic drugs.

The outcome of this project proposal include a tissue based model system, adequately reproducing both the healthy and diseased state of the intestinal tissue, providing a useful tool for studying and comparing the early epithelial events in different intestinal diseases. The model system may also be used for investigating cellular mechanisms of therapeutic drugs. The tissue based model system will in part replace experimental animal models exploring epithelial events of human intestinal diseases such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and colon cancer.

Senast uppdaterad: 13 oktober 2023