Human Histology and Biology and Clinical Applications of Stem Cells.
Learning outcomes of the course unit
The Course aims at imparting basic notions about the structure-function relationship of human tissues, how these are elaborated during development and the modes through which complex cellular and molecular interplays govern the conversion of a fertilized egg into a full organism. Students are therefore expected to gain a basic knowledge about the morphology, classification and functional peculiarities of the primary tissues of the body and how these can be examined in situ. The Students area also expected to gain a thorough understanding of the primary cellular phenomena controlling early embryonic development and how these may be regulated. Through the final part of the Course, Students will be instructed in the main biological and applicative features of adult stem cells, including their molecular and phenotypic characteristics, their differentiation potentials, the mechanisms controlling their fate and all these traits can be exploited in regenerative medicine. By also familiarizing with the technologies that may be used for analysing these phenomena and various aspects of cellular behaviour, the Students are further assured to reach full comprehension about how the acquired knowledge can be exploited in applied terms. Through the Course Students are further instructed in the ability to collect, compile and evaluate scientific information and data in the field such to be able to make proper judgements about their validity. This will be instrumental in their development of better communications and learning skills.
In relation to the first part of the Course, it is assumed that the Student has a sufficient background in cell biology and some of the techniques used to study cells. Effective following of the second part of the Course requires a solid background knowledge in cell and molecular biology and basic knowledge in biochemistry and genetics. Some minimal familiarity with basic immunology and pathology may also be of use.
Course contents summary
The Course is divided in two main parts (Modules): one dealing with the structural and functional characteristics of human tissues, from an histological standpoint (for a total of 3 CFU), and one treating fundamental aspects of Developmental Biology and adult stem cells, including their therapeutic potentials in approaches of regenerative medicine.
The Course starts with a survey of the methods, procedures and instruments used for examining the morphological characteristics of isolated tissues and cells, or cells in their natural environment (techniques for whole-body imaging), which in principle a repetition of the notions imparted through the Course of Cell Biology. In particular, this part of the Course treats the basics of the methods that may be used for staining cells and tissues in situ and/or tagging live cells for in vivo tracing. The Course then follows with the sequential description of the morphological-functional traits of the primary tissues of the human body, starting from the epithelial one and ending with the bone marrow, hematopoietic and vascular systems. Particular emphasis is given here to the embryonic origin of the tissues and how they have evolved during development of the embryo.
The second part of the Course (Module) related to Developmental Biology initiates with an overview of primary concepts, definition of widely used terms and the nomenclature currently adopted in the field. In the subsequent phase, the Course discusses the concept and modes of cleavage of the fertilized embryo, without entering into the detailed mechanisms, and the process of blastula formation. It proceeds with a treatment of the complex cellular, biochemical and molecular regulation of the specification of the three embryonic germ layers (endoderm, mesoderm and ectoderm) and the phenomenon of gastrulation. Particular attention is then given to the mechanisms controlling a number of other critical events ensuing early in the development: determination of the left-right symmetry, the dorso-ventral and the rostro-caudal polarities setting up for the body axis. It will then be possible to grasp the concept of cell fate determination and the molecular determinants of this phenomenon. Once clarified the process of neurulation, the Course focuses on the formation, migration and development of the neural crest cells and the formation of the peripheral nervous system. This part of the Course is concluded with the discussion of some basic notions of mesoderm segmentation and limb patterning and provides hints about fundamental processes underlying the formation of the central nervous system.
The final part of the Course addresses the discovery of the many types of stem cells and their tissue origin and distribution and the methods used to make these discoveries. Within this theme the Course approaches the biology of stem cells and more specifically the molecular bases for the self-renewal and multipotent differentiation capabilities.
Thereafter, the Course provides a further deepening of the effective differentiation patterns of the primary types of stem cells of the adult human body and how these can be exploited for clinical applications. It dwells upon this issue by discussing the prototype stem cell – “the hematopoietic stem cell” identified by surface expression of CD34. Mesenchymal, neural and cardiac stem cells are then treated In an analogous way with particular emphasis on the highlighting of the areas of regenerative medicine in which these cells could be valuable. Even in the case of the above stem cells a goal of the Course is to reference the initial discoveries of the origin and developmental potential of the cells. The final part of the Course concentrates on the recent revolutionary findings on cellular reprogramming and the creation of IPs cells – Induced Pluripotent Stem cells – (a topic that has lead S. Yamanaka and J.B. Gurdon to receive the Nobel Price in 2012).
The Course Module “Functional Histology” entails the following topics:
1. Methods, instruments and approaches for the analysis of tissue structure and composition;
2. Classification, structural diversity and functional characteristics of epithelial tissues;
3. Classification and structural-functional traits of connective tissues and their associated extracellular matrix;
4. Classification and characteristics of specialized connective tissues;
5. The hematopoietic system and the cellular elements of blood;
6. The main characteristics of the vascular structures;
Chapters of the recommended text book "Histology: A Text and Atlas", by Micheal H. Ross e Wojciech Pawlina related to the above topics are the following:
Chapter 1 – “Methods”
Chapter 4 – “Tissues: concepts and classification”
Chapter 5 – “Epithelial tissue”
Chapter 6 – “Connective tissue”
Chapter 7 – “Cartilage”
Chapter 8 – “Bone”
Chapter 9 – “Adipose tissue”
Chapter 10 – “Blood”
The Course Module “Developmental Biology” entails the following topics:
1. Terminology and concepts
2. The process of cleavage and gastrulation
3. Specification of the germ layers: endoderm, mesoderm and ectoderm
4. Establishment of the dorsal-ventral polarity
5. Establishment of the anterior-posterior body axis
6. Establishment of the left-right asymmetry
7. The default state of neural induction
8. The process of neurulation
9. Formation and development of the neural crest
10. Formation of the central nervous system
11. Molecular control of the establishment of the body plan – the “Hox code”
The chapters of the recommended primary text book, “Principle of Development” by Wolpert and co-authors, pertaining to these topics are:
Chapter 1 - History and basic concepts
Chapter 3 - Vertebrate development I: life cycles and experimental techniques
Chapter 4 - Vertebrate development II: Xenopus and zebrafish
Chapter 5 - Vertebrate development III: Chick and mouse - completing the body plan
Chapter 9 - Morphogenesis: change in form in the early embryo
Chapter 12 - Development of the nervous system
Relevant Chapters from the supportive, complementary text book “Developmental Biology” by Gilbert and Barresi include:
I. PATTERNS AND PROCESSES OF BECOMING: A FRAMEWORK FOR UNDERSTANDING ANIMAL DEVELOPMENT
2. Specifying Identity: Mechanisms of Developmental Patterning
Levels of Commitment
A Rainbow of Cell Identities
4. Cell-to-Cell Communication: Mechanisms of Morphogenesis
A Primer on Cell-to-Cell Communication
Adhesion and Sorting: Juxtacrine Signaling and the Physics of Morphogenesis
The Extracellular Matrix as a Source of Developmental Signals
The Epithelial-Mesenchymal Transition
Paracrine Factors: Inducer Molecules
The Cell Biology of Paracrine Signaling
Juxtacrine Signaling for Cell Identity
III. EARLY DEVELOPMENT: CLEAVAGE, GASTRULATION, AND AXIS FORMATION
11. Amphibians and Fish
EARLY AMPHIBIAN DEVELOPMENT
Fertilization, Cortical Rotation, and Cleavage
Progressive Determination of the Amphibian Axes
The Work of Hans Spemann and Hilde Mangold
Molecular Mechanisms of Amphibian Axis Formation
Regional Specificity of Neural Induction along the Anterior-Posterior Axis
Specifying the Left-Right Axis
12. Birds and Mammals
EARLY DEVELOPMENT IN BIRDS
Gastrulation of the Avian Embryo
Axis Specification and the Avian "Organizer"
EARLY DEVELOPMENT IN MAMMALS
Mammalian Axis Formation
IV. BUILDING WITH ECTODERM: THE VERTEBRATE NERVOUS SYSTEM AND EPIDERMIS
13. Neural Tube Formation and Patterning
Transforming the Neural Plate into a Tube: The Birth of the Central Nervous System
Patterning the Central Nervous System
All Axes Come Together
14. Brain Growth
Neuroanatomy of the Developing Central Nervous System
Developmental Mechanisms Regulating Brain Growth
Development of the Human Brain
15. Neural Crest Cells and Axonic Specificity
THE NEURAL CRES
The recommended text book for the first part of the Course is "Histology: A Text and Atlas", by Micheal H. Ross and Wojciech Pawlina, published by Lippincott Williams & Wilkins. As the Course teaches ground level notions of functional histology, there are a numerous other books that the Students may consult to grasp the same concepts. Students may therefore opt for the adoption of an alternative text book for their studies, but should be aware of the fact that lectures and the final examination will strictly follow the above mentioned book by Ross and Pawlina.
For the second part of the Course, the recommended text book is 4th edition of “Principles of Development”, by Lewis Wolpert and Cheryll Tickle, and the contribution by a number of other authors (Oxford University Press). Students are also encouraged to consult the 11th edition of “Developmental Biology” by Scott Gilbert as a complementary text book. A copy of the presentations given through the Lectures is made available through the institutional web platform “Elly”.
To reach the Course’s objective, that is, to transmit to the student a comprehensive understanding of the morpho-functional characteristics of human tissues, how they are created during development and how embryonic development is regulated at the cellular and molecular level, the Course literature has been selected such as to offer the most modern and up-to-date texts treating these matters. As the field of developmental biology is pervaded by experimental milestone articles published in scientific journals of major impact, landmarks discoveries are extensively treated during the Lectures, often by using images from the original publications as an aid. Particular care is therefore taken to complement illustrations of the text books with authentic illustration, while assuring that this material is readily accessible to the Students.
When it comes to the module of the Course dealing with stem cells, Lectures are exclusively based on presentations Because of this invaluable contribution made by the Lecturer and afforded by his knowledge and scientific experience in the field, it is strongly recommended that the Students attend ALL lectures and access notes taken by course mates in case of unattendance. Students are also given the opportunity to improve their ability to recognize human tissues by a dedicated training of sample analysis offered collectively through representative tissue slides. Thus, the Course entails both traditional lecturing and some more interactive events.
Assessment methods and criteria
Attendance of the Course is mandatory and Students are therefore highly encouraged to take part at the Lectures. In case of absence, Students should make sure to access the Course mates’ notes from unattended Lectures. Course proficiency evaluation involves the combined evaluation of a written exam for the Course Module related to "Functional Histology" and an oral presentation for the Course Module related to the "Developmental Biology and Stem Cells". The score obtained for this latter presentation weights more (in the ratio of 70% versus 30%) than former for the assignment of the final score, consistently with the different amounts of CFUs accounted for each of the Modules of the Course.
The written exam for the "Functional Histology" part of the Course is based upon 8 open questions, each receiving a maximum of 4 points, for a total of 32 points. There is no limit in the number of times that the test can be repeated if a minimum of 18 points is not reached. Conversely, the test cannot be repeated if the score obtained is equal to or above 18 points.
The examination of the part of the Course related to "Developmental Biology/Stem Cells " requires the delivery of a short Presentation on a topic autonomously and independently selected by the Student and strongly pertaining to the topics discussed during the Course. The Student is therefore called in to select a subject of his/her particular interest and compile a suitable Presentation of that subject. The Presentation is judged for its quality in terms of clarity, accurateness and pertinence to the selected topic. Particular attention is given to the degree of knowledge of the Student on the selected subject and how he/she articulates it. The Presentation should not exceed 5 minutes and is followed by a short discussion related to the Presentation as well as intended to assess the Student’s basic knowledge on the subject of the Course. If the Presentation is judged to be of insufficient quality and receives a low score (vote), it is possible to give another one, in a different occasion and on a different topic. This should similarly be selected autonomously by the Student.
As a thumb rule, the Presentation should entail no more than 5 slides, which should be illustrative and NOT simply report copied texts from books or articles. This means that slides should mostly report tables, graphs, images, diagrams and schemes, which may be supported by short explanatory texts. As a guideline, the Presentation should give an overview of what is currently known about the topic that is dealt, but may also treat a few up-to-date scientific articles describing highly innovative findings that may be particularly important for the field. Negative evaluations will be given to Presentations on subjects not related to the topic specifically selected by the Student; Presentations that are excessively long; Presentations that do not respect the above guidelines of how they should be organized; and Presentations that do not provide a sufficiently clear Comprehensive view on the treated subject will similarly be judged negatively.
Evaluation of the part related to “Stem Cells” is based upon a discussion related to one of the topics treated during the Course. Examples of subjects that could be selected by the Lecturer for this discussion is provided below.
Topics upon which basing the presentation related to the Course Module "Biology and clinical applications of stem cells" is provided separately on the web Platform Elly.
The first part of the Course dealing with functional histology is organically coordinated with the parallel Course in Human Anatomy and Histology held by Prof. Cecilia Carubbi. Hence, histological characteristics of different tissues are treated separately, but in a complementary manner, by the two courses.