In vitro and in vivo model systems for human diseases modeling
A.A. 2025/2026
Obiettivi formativi
The course aims to provide students with an in-depth understanding of the use of experimental disease models in biomedical research. It will explore the rationale behind using animal and patient-derived models, their contributions to scientific advancements, and the ethical and regulatory considerations associated with their use.
Through this course, students will:
· Gain a historical and conceptual understanding of animal models, with a focus on genetically engineered mice and their role in biomedical research.
· Understand the application of transgenic mouse models, including knock-in, knock-out, and CRISPR/Cas9-mediated genome editing techniques.
· Analyze the role of mouse models in cancer research, from tumor initiation to preclinical drug evaluation.
· Explore patient-derived experimental disease models, including the development and applications of induced pluripotent stem cells (iPSCs).
· Study the use of mouse models for neuromuscular diseases, metabolic disorders (such as diabetes and obesity), and immunological conditions (autoimmune diseases and immunodeficiencies).
· Examine the pathogenetic mechanisms of diseases in animal models, including the role of the microbiota in immunity, metabolism, and inflammatory conditions.
· Learn about cutting-edge approaches in patient-derived disease modeling, such as 3D organoids, organ-on-chip technology, and AI-driven personalized medicine strategies.
· Acquire a comprehensive understanding of ethical considerations and regulatory guidelines, including the 3R principles (Replacement, Reduction, and Refinement) in animal research.
By the end of the course, students will be equipped with the necessary knowledge to critically assess and apply disease models in biomedical research, contributing to the development of innovative therapies and personalized medicine.
Through this course, students will:
· Gain a historical and conceptual understanding of animal models, with a focus on genetically engineered mice and their role in biomedical research.
· Understand the application of transgenic mouse models, including knock-in, knock-out, and CRISPR/Cas9-mediated genome editing techniques.
· Analyze the role of mouse models in cancer research, from tumor initiation to preclinical drug evaluation.
· Explore patient-derived experimental disease models, including the development and applications of induced pluripotent stem cells (iPSCs).
· Study the use of mouse models for neuromuscular diseases, metabolic disorders (such as diabetes and obesity), and immunological conditions (autoimmune diseases and immunodeficiencies).
· Examine the pathogenetic mechanisms of diseases in animal models, including the role of the microbiota in immunity, metabolism, and inflammatory conditions.
· Learn about cutting-edge approaches in patient-derived disease modeling, such as 3D organoids, organ-on-chip technology, and AI-driven personalized medicine strategies.
· Acquire a comprehensive understanding of ethical considerations and regulatory guidelines, including the 3R principles (Replacement, Reduction, and Refinement) in animal research.
By the end of the course, students will be equipped with the necessary knowledge to critically assess and apply disease models in biomedical research, contributing to the development of innovative therapies and personalized medicine.
Risultati apprendimento attesi
At the end of the course, students will have acquired a comprehensive understanding of experimental disease models in biomedical research. The learning outcomes include knowledge acquisition, practical application, critical thinking, communication skills, and independent learning abilities.
1. Knowledge acquisition
Students will:
· Understand the historical and scientific rationale behind the use of animal models in biomedical research, including their strengths and limitations.
· Gain in-depth knowledge of genetically engineered mouse models, including transgenic, knock-in, knock-out, and CRISPR/Cas9-based genome editing techniques.
· Learn about the application of mouse models in cancer research, neurodegenerative diseases, metabolic disorders, and immunological conditions.
· Understand the significance of patient-derived experimental disease models, including iPSCs, 3D organoids, and organ-on-chip technologies.
· Explore ethical considerations and regulatory guidelines, including the 3R principles and legislation governing the use of animal models in research.
2. Application of knowledge and understanding:
Students will:
· Apply their knowledge to design and critically evaluate experimental disease models for preclinical research.
· Analyze the advantages and limitations of different modeling approaches in addressing specific biomedical questions.
· Comprehend how metabolic/microbiota profiling and preclinical drug testing strategies can be used to study disease progression and therapeutic responses.
· Interpret and integrate multi-omics data into patient-derived models to identify disease-specific biomarkers and therapeutic targets.
· Consider ethical and regulatory aspects when designing and implementing in vivo and in vitro experiments.
3. Critical thinking
Students will:
· Develop the ability to critically assess the validity and applicability of animal and patient-derived models in biomedical research.
· Evaluate the ethical implications of using experimental models, balancing scientific progress with animal welfare concerns.
· Formulate independent opinions on the future directions of disease modeling, including emerging technologies and alternative approaches.
4. Communication skills
Students will:
· Be able to clearly communicate complex biomedical concepts related to experimental disease models to both specialized and non-specialized audiences.
· Develop the ability to present research findings effectively through oral presentations.
· Engage in scientific discussions, demonstrating an ability to interpret, critique, and synthesize relevant literature.
5. Learning abilities
Students will:
· Acquire autonomous learning skills, enabling them to stay updated on new advancements in biomedical research and experimental modeling.
· Develop a multidisciplinary approach, integrating knowledge from genetics, oncology, immunology, microbiology, neurology, stem cell biology and bioengineering.
· Enhance their ability to adapt to evolving research methodologies, including the integration of artificial intelligence and machine learning in personalized medicine.
By achieving these learning outcomes, students will be well-prepared to contribute to biomedical research, with competencies that support careers in academia, industry, and translational medicine.
1. Knowledge acquisition
Students will:
· Understand the historical and scientific rationale behind the use of animal models in biomedical research, including their strengths and limitations.
· Gain in-depth knowledge of genetically engineered mouse models, including transgenic, knock-in, knock-out, and CRISPR/Cas9-based genome editing techniques.
· Learn about the application of mouse models in cancer research, neurodegenerative diseases, metabolic disorders, and immunological conditions.
· Understand the significance of patient-derived experimental disease models, including iPSCs, 3D organoids, and organ-on-chip technologies.
· Explore ethical considerations and regulatory guidelines, including the 3R principles and legislation governing the use of animal models in research.
2. Application of knowledge and understanding:
Students will:
· Apply their knowledge to design and critically evaluate experimental disease models for preclinical research.
· Analyze the advantages and limitations of different modeling approaches in addressing specific biomedical questions.
· Comprehend how metabolic/microbiota profiling and preclinical drug testing strategies can be used to study disease progression and therapeutic responses.
· Interpret and integrate multi-omics data into patient-derived models to identify disease-specific biomarkers and therapeutic targets.
· Consider ethical and regulatory aspects when designing and implementing in vivo and in vitro experiments.
3. Critical thinking
Students will:
· Develop the ability to critically assess the validity and applicability of animal and patient-derived models in biomedical research.
· Evaluate the ethical implications of using experimental models, balancing scientific progress with animal welfare concerns.
· Formulate independent opinions on the future directions of disease modeling, including emerging technologies and alternative approaches.
4. Communication skills
Students will:
· Be able to clearly communicate complex biomedical concepts related to experimental disease models to both specialized and non-specialized audiences.
· Develop the ability to present research findings effectively through oral presentations.
· Engage in scientific discussions, demonstrating an ability to interpret, critique, and synthesize relevant literature.
5. Learning abilities
Students will:
· Acquire autonomous learning skills, enabling them to stay updated on new advancements in biomedical research and experimental modeling.
· Develop a multidisciplinary approach, integrating knowledge from genetics, oncology, immunology, microbiology, neurology, stem cell biology and bioengineering.
· Enhance their ability to adapt to evolving research methodologies, including the integration of artificial intelligence and machine learning in personalized medicine.
By achieving these learning outcomes, students will be well-prepared to contribute to biomedical research, with competencies that support careers in academia, industry, and translational medicine.
Periodo: Terzo trimestre
Modalità di valutazione: Esame
Giudizio di valutazione: voto verbalizzato in trentesimi
Corso singolo
Questo insegnamento non può essere seguito come corso singolo. Puoi trovare gli insegnamenti disponibili consultando il catalogo corsi singoli.
Programma e organizzazione didattica
Edizione unica
Responsabile
Periodo
Terzo trimestre
Programma
The course is structured into different modules, each focusing on key aspects of experimental disease models in biomedical research. It will cover animal models and patient-derived models, exploring their applications in various disease contexts, as well as ethical and regulatory considerations.
Module 1: Animal Models in biomedical research: Prof Casola
1.1. Definition of a model system
· Uni- vs. multi-cellular models
· In vitro, in vivo, ex vivo models
· Requisites
· Applications
· Advantages and limitations
1.2. Uni-cellular model systems and their relevance in fundamental discoveries
· Prokaryotes: the birth of molecular genetics
· Yeast: the cell-cycle, protein secretion machinery and autophagy
1.3. Multicellular model systems: animal models-I (genetics, applications, advantages and limitations)
· Caenorhabditis Elegans
· Drosophila Melanogaster
· Danio Rerio
· Xenopus Laevis
1.4. Multicellular model systems: animal models-II: the laboratory mouse Mus musculus.
· Genetic engineering in the mouse model
· Fundamentals in gene targeting
· Transgenesis
· Site-directed gene mutagenesis
· Conditional gene targeting
· Tools (Cre/loxP, transposases, lenti/adeno/adeno-associated viruses)
· Tissue- and stage specific gene regulation in vivo
· Time-controlled gene regulation in vivo
· How to design an experiment with conditional gene targeted mice
· Limitations and risks
1.5. Which cells do we target in the mouse?
· The 2-cell stage embryo
· Embryonic stem cells
· Adult stem cells
· Somatic cells
1.6. CRISPR/Cas9 gene editing in vivo: methods and clinical applications.
· How does it work?
· Which cells do we target?
· Homology-directed repair to build precise animal/cellular models of human diseases.
· Cas9 variants and their applications
· What should we worry about using Cas9 technology?
· Clinical applications: congenital disorders, cancer immunity
1.7. Monitoring gene function in animal models: tools.
· Gene reporters
· Histology
· Flow cytometry
· Time lapse live cell imaging
· Single cell RNA sequencing
· Spatial transcriptomics
· Proteomics
1.8. Studying cancer in genetically engineered mouse models.
· Human cancer genetics: drivers vs passengers
· Reproducing cancer genetics in the mouse model: conventional versus conditional mouse models
· Discovering cancer genes through forward genetic screenings: from chemical mutagenesis to the use of mobile elements
· Monitoring cancer development in the mouse model: from histopathology to live cell imaging
1.9. Humanized animal models. Prof S. Casola
· Humanizing the immune system of mice: tools and applications
· Engineering mice to produce human antibodies
· Patient-derived xenografts
· The chick embryo platform for anti-cancer immunotherapies
1.10. Cell reprogramming and induced Pluripotent Stem Cells (iPS) in regenerative medicine.
· Historical notes
· Genetic engineering
· In vitro differentiation
· Clinical applications in regenerative medicine
Module 2: Specialized animal models in experimental medicine: Prof C. De Palma
2.1. Mouse models of neuromuscular inherited diseases
· Experimental tools for studying neuromuscular disorders
· Therapeutic interventions and drug testing
2.2. Modeling metabolic diseases
· Experimental models for diabetes and obesity
· Metabolic phenotyping techniques
· Targeting metabolic pathways for therapeutic development
2.3. Ethical considerations and regulatory guidelines in animal experimentation
· Legislation on animal research
· 3R principles
Module 3: Immunological and microbiota-related disease models: Prof. F. Grassi
3.1 Mouse models of immunological disorders
· Classification of primary immunodeficiencies
· Understanding immune system function by mouse modeling of primary immunodeficiencies
· Immune system dysregulation in primary immunodeficiencies
· Pathogenetic mechanisms in immunopathological conditions
3.2 Anti-cancer Immunotherapies in animal models
· Translational value of mouse models in cancer immunotherapy
· Mechanisms conditioning cancer immunotherapies by mouse modeling
· Preclinical evaluation of immune-based therapeutics
3.3. Role of the microbiota in disease modeling
· The gut microbiota at the interface of immune system and metabolism
· Microbiota and inflammatory diseases
· Microbiota in cancer development and therapy response
Module 4: Patient-Derived Experimental Disease Models: Prof Pagani
4.1. 3D organoid models in biomedical research
· Development and applications of 3D organoid and tumoroid models
· Enhancing cellular complexity in organoid systems
· Tissue explant cultures
4.2. Applications of Patient-Derived Models
· Recapitulating disease phenotypes and progression
· Drug screening and personalized medicine approaches
· Identification of disease-specific markers and therapeutic targets
4.3. Future innovations in disease modeling
· Advancements in organ-on-chip models
· Integration of multi-omics data for disease modeling
· Artificial intelligence and machine learning in personalized medicine
Teaching methods
· Lectures: Theoretical lessons on key concepts and methodologies
· Practical Discussions: Ethical and regulatory debates on experimental models
· Research Analysis: Reviewing and discussing recent scientific literature
This syllabus ensures a progressive and comprehensive learning experience, providing students with both conceptual knowledge and practical insights into disease modeling for biomedical research.
Module 1: Animal Models in biomedical research: Prof Casola
1.1. Definition of a model system
· Uni- vs. multi-cellular models
· In vitro, in vivo, ex vivo models
· Requisites
· Applications
· Advantages and limitations
1.2. Uni-cellular model systems and their relevance in fundamental discoveries
· Prokaryotes: the birth of molecular genetics
· Yeast: the cell-cycle, protein secretion machinery and autophagy
1.3. Multicellular model systems: animal models-I (genetics, applications, advantages and limitations)
· Caenorhabditis Elegans
· Drosophila Melanogaster
· Danio Rerio
· Xenopus Laevis
1.4. Multicellular model systems: animal models-II: the laboratory mouse Mus musculus.
· Genetic engineering in the mouse model
· Fundamentals in gene targeting
· Transgenesis
· Site-directed gene mutagenesis
· Conditional gene targeting
· Tools (Cre/loxP, transposases, lenti/adeno/adeno-associated viruses)
· Tissue- and stage specific gene regulation in vivo
· Time-controlled gene regulation in vivo
· How to design an experiment with conditional gene targeted mice
· Limitations and risks
1.5. Which cells do we target in the mouse?
· The 2-cell stage embryo
· Embryonic stem cells
· Adult stem cells
· Somatic cells
1.6. CRISPR/Cas9 gene editing in vivo: methods and clinical applications.
· How does it work?
· Which cells do we target?
· Homology-directed repair to build precise animal/cellular models of human diseases.
· Cas9 variants and their applications
· What should we worry about using Cas9 technology?
· Clinical applications: congenital disorders, cancer immunity
1.7. Monitoring gene function in animal models: tools.
· Gene reporters
· Histology
· Flow cytometry
· Time lapse live cell imaging
· Single cell RNA sequencing
· Spatial transcriptomics
· Proteomics
1.8. Studying cancer in genetically engineered mouse models.
· Human cancer genetics: drivers vs passengers
· Reproducing cancer genetics in the mouse model: conventional versus conditional mouse models
· Discovering cancer genes through forward genetic screenings: from chemical mutagenesis to the use of mobile elements
· Monitoring cancer development in the mouse model: from histopathology to live cell imaging
1.9. Humanized animal models. Prof S. Casola
· Humanizing the immune system of mice: tools and applications
· Engineering mice to produce human antibodies
· Patient-derived xenografts
· The chick embryo platform for anti-cancer immunotherapies
1.10. Cell reprogramming and induced Pluripotent Stem Cells (iPS) in regenerative medicine.
· Historical notes
· Genetic engineering
· In vitro differentiation
· Clinical applications in regenerative medicine
Module 2: Specialized animal models in experimental medicine: Prof C. De Palma
2.1. Mouse models of neuromuscular inherited diseases
· Experimental tools for studying neuromuscular disorders
· Therapeutic interventions and drug testing
2.2. Modeling metabolic diseases
· Experimental models for diabetes and obesity
· Metabolic phenotyping techniques
· Targeting metabolic pathways for therapeutic development
2.3. Ethical considerations and regulatory guidelines in animal experimentation
· Legislation on animal research
· 3R principles
Module 3: Immunological and microbiota-related disease models: Prof. F. Grassi
3.1 Mouse models of immunological disorders
· Classification of primary immunodeficiencies
· Understanding immune system function by mouse modeling of primary immunodeficiencies
· Immune system dysregulation in primary immunodeficiencies
· Pathogenetic mechanisms in immunopathological conditions
3.2 Anti-cancer Immunotherapies in animal models
· Translational value of mouse models in cancer immunotherapy
· Mechanisms conditioning cancer immunotherapies by mouse modeling
· Preclinical evaluation of immune-based therapeutics
3.3. Role of the microbiota in disease modeling
· The gut microbiota at the interface of immune system and metabolism
· Microbiota and inflammatory diseases
· Microbiota in cancer development and therapy response
Module 4: Patient-Derived Experimental Disease Models: Prof Pagani
4.1. 3D organoid models in biomedical research
· Development and applications of 3D organoid and tumoroid models
· Enhancing cellular complexity in organoid systems
· Tissue explant cultures
4.2. Applications of Patient-Derived Models
· Recapitulating disease phenotypes and progression
· Drug screening and personalized medicine approaches
· Identification of disease-specific markers and therapeutic targets
4.3. Future innovations in disease modeling
· Advancements in organ-on-chip models
· Integration of multi-omics data for disease modeling
· Artificial intelligence and machine learning in personalized medicine
Teaching methods
· Lectures: Theoretical lessons on key concepts and methodologies
· Practical Discussions: Ethical and regulatory debates on experimental models
· Research Analysis: Reviewing and discussing recent scientific literature
This syllabus ensures a progressive and comprehensive learning experience, providing students with both conceptual knowledge and practical insights into disease modeling for biomedical research.
Prerequisiti
Students enrolling in this course are expected to have a foundational understanding of biomedical sciences, including basic concepts in cell biology, genetics, and molecular biology. A general familiarity with biotechnology and pathology will be beneficial for comprehending the topics covered in experimental disease modeling.
While no specific prerequisites beyond those required for admission to the degree program are mandatory, prior knowledge in the following areas is recommended to facilitate learning:
· Genetics and molecular biology (e.g., gene expression, DNA recombination, genome editing techniques)
· Basic immunology and oncology (e.g., immune system function, tumor biology)
· Biotechnology applications in biomedical research
For students who may not have a strong background in these subjects, additional self-study resources and introductory materials will be suggested to support their learning throughout the course.
While no specific prerequisites beyond those required for admission to the degree program are mandatory, prior knowledge in the following areas is recommended to facilitate learning:
· Genetics and molecular biology (e.g., gene expression, DNA recombination, genome editing techniques)
· Basic immunology and oncology (e.g., immune system function, tumor biology)
· Biotechnology applications in biomedical research
For students who may not have a strong background in these subjects, additional self-study resources and introductory materials will be suggested to support their learning throughout the course.
Metodi didattici
The course will be delivered through a combination of lectures and interactive discussions to provide students with a comprehensive understanding of experimental disease models. The teaching methods are designed to enhance both theoretical knowledge and practical application, fostering critical thinking and active participation.
Teaching
Lectures: front-facing teaching
· The core concepts of the course will be introduced through structured lectures, ensuring a solid understanding of animal and patient-derived experimental models.
· Lectures will include visual aids such as slides and videos to enhance comprehension.
Interactive discussions:
· Students will be encouraged to engage in discussions on scientific literature, ethical considerations, and real-world applications of experimental models.
· Selected articles will be analyzed to illustrate the advantages, limitations, and translational potential of different disease models.
Group work and presentations (Optional):
Students may be divided into small groups to research specific topics, prepare a brief analysis, and present their findings in class.
This collaborative approach enhances teamwork, critical evaluation, and communication skills.
Practical Learning and Digital Resources:
· The course will integrate digital resources and e-learning materials, including scientific articles, video tutorials, and supplementary readings available on the MyAriel platform.
· Some lessons may include demonstrations of experimental methodologies used in disease modeling.
Attendance is strongly recommended to ensure full understanding of the course material, as interactive discussions and case study analysis represent an integral part of the learning experience.
Students who are unable to attend regularly will have access to course materials and supplementary readings via MyAriel.
This teaching methodology aims to ensure an engaging and comprehensive learning experience, equipping students with both theoretical knowledge and practical skills necessary for biomedical research.
Teaching
Lectures: front-facing teaching
· The core concepts of the course will be introduced through structured lectures, ensuring a solid understanding of animal and patient-derived experimental models.
· Lectures will include visual aids such as slides and videos to enhance comprehension.
Interactive discussions:
· Students will be encouraged to engage in discussions on scientific literature, ethical considerations, and real-world applications of experimental models.
· Selected articles will be analyzed to illustrate the advantages, limitations, and translational potential of different disease models.
Group work and presentations (Optional):
Students may be divided into small groups to research specific topics, prepare a brief analysis, and present their findings in class.
This collaborative approach enhances teamwork, critical evaluation, and communication skills.
Practical Learning and Digital Resources:
· The course will integrate digital resources and e-learning materials, including scientific articles, video tutorials, and supplementary readings available on the MyAriel platform.
· Some lessons may include demonstrations of experimental methodologies used in disease modeling.
Attendance is strongly recommended to ensure full understanding of the course material, as interactive discussions and case study analysis represent an integral part of the learning experience.
Students who are unable to attend regularly will have access to course materials and supplementary readings via MyAriel.
This teaching methodology aims to ensure an engaging and comprehensive learning experience, equipping students with both theoretical knowledge and practical skills necessary for biomedical research.
Materiale di riferimento
Lecturer's will provide students with bibliographical material during the course while progressing through the topics.
Modalità di verifica dell’apprendimento e criteri di valutazione
The assessment of student learning outcomes will be conducted through an oral examination to gain a comprehensive evaluation of knowledge, application skills, and critical thinking.
Format: individual oral examination
Content:
· Discussion on topics covered in the course, assessing knowledge and understanding of experimental disease models.
· Application of concepts to biomedical research scenarios (e.g., justifying the choice of a particular disease model for a research question).
· Critical analysis of ethical and regulatory considerations in disease modeling.
Evaluation criteria:
· Ability to organize and articulate knowledge cohesively
· Scientific accuracy and depth of understanding
· Critical thinking and problem-solving skills
· Quality of exposition, use of specialized terminology, and argumentation skills
Format: individual oral examination
Content:
· Discussion on topics covered in the course, assessing knowledge and understanding of experimental disease models.
· Application of concepts to biomedical research scenarios (e.g., justifying the choice of a particular disease model for a research question).
· Critical analysis of ethical and regulatory considerations in disease modeling.
Evaluation criteria:
· Ability to organize and articulate knowledge cohesively
· Scientific accuracy and depth of understanding
· Critical thinking and problem-solving skills
· Quality of exposition, use of specialized terminology, and argumentation skills
BIO/11 - BIOLOGIA MOLECOLARE - CFU: 1
BIO/13 - BIOLOGIA APPLICATA - CFU: 1
BIO/14 - FARMACOLOGIA - CFU: 1
MED/04 - PATOLOGIA GENERALE - CFU: 3
BIO/13 - BIOLOGIA APPLICATA - CFU: 1
BIO/14 - FARMACOLOGIA - CFU: 1
MED/04 - PATOLOGIA GENERALE - CFU: 3
Lezioni: 42 ore
Turni:
Docente/i
Ricevimento:
Via Fratelli Cervi 93, Segrate (Mi), previo appuntamento da concordare via e-mail
Ricevimento:
previo appuntamento da concordare via e-mail