Learning objectives
The Course "Histology of Human Tissues and Biology and Clinical Applications of Stem Cells', abbreviated ITUBACCS ("Istologia dei Tessuti Umani, Biologia e Applicazioni Cliniche delle Cellule Staminali"), represents a unique and highly innovative Course within the Italian University System. It is an interactive Course open to students of the second level of education, or higher, and is characterized by an integration of functional histology and the biology of stem cells.
While solidly dwelling upon the fundamentals of the structure and organization of human tissues, the Course aims at imparting notions about the functional and molecular bases for the architecture, maintenance and remodeling of tissues and how this is assured by the purporting of the stem/progenitor cells residing in specific niches. The Course has therefore the objective to allow students to acquire a comprehensive view of how homeostasis of human tissues is controlled by a delicate balance between a precise arrangement of their cellular and extracellular matrix elements and the regeneration capabilities that the endogenous progenitor/stem cells may possess. Ultimately, the student is expected to gain a global understanding of the intimate association between tissue structure (morphology) and homeostatic dynamics (function).
To ascertain that students will grasp the elementary notions about the above mentioned structure-functional relationship governing tissue homeostasis, the Course discusses conventional and more advanced methods for the analysis of tissue and extracellular matrix assembly, the modes of maintenance of such structures, and the mechanisms governing tissue regeneration. How stem/progenitor cells may contribute to these processes will be at the focus of attention. The Course has thereby the following primary goals:
I. impart basic notions about morphology, cellular organization and molecular characteristics of human tissues;
II. discuss in detail the endogenous regeneration capabilities of different human tissues/organs;
III. discuss in detail the cellular and molecular traits of the different stem cell populations discovered in the various tissues/organs of the human body;
IV. treat the functional properties of these cells and how such properties have been, or can be, established experimentally;
V. exemplify how various stem cell types may be exploited in therapeutic settings for tissue reconstruction approaches and for the treatment of a variety of pathological conditions, including chronic inflammation, degenerative and autoimmune diseases, and cancer.
Prerequisites
To effectively be able to follow the lectures of the second part of the Course it is requested to possess a solid background knowledge in cell biology and basic knowledge about the most elementary developmental biological concepts. The student would also strongly benefit from being familiar with principles of biochemistry, molecular biology, immunology, genetics, anatomy and general pathology, as well as have previously been confronted with all primary laboratory techniques within the field of life sciences.
Course unit content
The Course starts with a thorough discussion of the methods, procedures and instruments used for examining the morphological characteristics of isolated tissues and cells, or cells within their natural environment (techniques for whole-body imaging). This first part treats methods for staining cells and tissues in situ and tagging of 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 and hematopoietic system. Particular emphasis is given here to the fact that some tissues have been discovered to have a higher spontaneous regeneration capacity than previously thought and what the homoestatic consequences of this ability could be.
The second part of the Course is focalized on stem cells and is initiated with an overview of primary concepts, definition of widely used terms, and the presentation of currently adopted nomenclature in the field. In the subsequent phase, the Course discusses the discovery of stem/progenitor cells in most tissues/organs of the human body, the putative evolutionary conservation of this distribution, and the methods that have led to these findings.
More detailed molecular aspects of stem cell biology are initially approached by a detailed explanation of the phenomenon of asymmetric cell division and its biological significance, as well as how it relates to the process of self-renewal and multipotency. Our current knowledge about the characteristics and clinical potentials of the primary stem cells of the human body are then treated starting with the "prototype" stem cell - the hematopoietic CD34+ stem cell.
A fair amount of the Course is dedicated to the understanding of the biological and functional properties of mesenchymal progenitor/stem cells of the bone marrow, adipose tissue and placenta, the experimental approaches that have been adopted to define this properties and how these cells are exploited in regenerative medicine, palliative treatments, anti-neoplastic therapies, and cell transplantation approaches in support of such therapies.
Other stem cells that are extensively discussed include the heart resident ones, the circulating endothelial precursors and the epithelial stem cells, making an effort to impart of a comprehensive view of how these cells were originally identified, how their biological behaviour has been unfolded and how the potential of these cells is believed to exploitable in tissue/organ regeneration approaches. A this point, the Course discusses the characteristics of embryonic stem cells, the differences between these and the adult stem cells, their potential for better understanding basic molecular mechanisms of cell differentiation and phenotypic diversification, including the epigenetic control of this phenomenon, and the promises and limitations of their potential use for clinical applications.
The final part of the Course is dedicated to approaches genetic reprogramming of cells and tissues and these approaches culminated in the discovery of how to reprogram by molecular means somatic cells (iPS cells - induced Pluripotent Stem cells). In the context some time is spent describing the advances made in the reprogramming technology to make more effective, safer and adaptable to clinical implementation.
Full programme
When treating the different subjects related to the biology of stem cells, particular care is taken to highlight pitfalls in the approaching of the nature and biological potential of stem cells and how a number of acclaimed studies were later on found to be false and/or non reproducible and/or forged by false interpretations of the data. In this context, the Course touches upon the phenomenon of cell fusion and how this may affect the biological behaviour of stem cells. A number of lectures are then devoted to the understanding of the functional traits of neural stem cells and how the fetal ones could be employed in regenerative medicine. Other types of stem cells that are extensively discussed included the heart resident ones, the circulating endothelial precursors and the epithelial stem cells, with specific emphasis on the intestinal ones. Even in these cases, the Course assures the imparting of a comprehensive view of how these cells were originally identified, how their biological behaviour has been unfolded and how the potential of these cells is believed to exploitable in tissue/organ regeneration strategies.
Finally, the Course discusses the characteristics of embryonic stem cells, the differences between these and the adult stem cells, their potential for better understanding basic molecular mechanisms of cell differentiation and phenotypic diversification, including the epigenetic control of this phenomenon, and the promises and limitations of their potential use for clinical applications. The final part of the Course is dedicated to the "Nobel prize-winning" topic of the iPS cells - induced Pluripotent Stem cells – that was introduced in 2006 by Shinya Yamanaka and how his discovery of “reprogramming factors” relates to the nuclear reprogramming approach originally documented in Xenopus by Sir John B. Gurdon. A certain amount of time is then dedicated to the milestone discoveries of Rudolph Jaenish and the observations made by the Nobel Laureate Sir Martin Evans on teratomas.
The comprehensive list of topics discussed during the Course include:
1. General characteristics of stem cells: definitions, nomenclature, tissue localization and methods of identification;
2. Characteristics of the stem cell niches and their significance;
3. Methods for studying stem cells in vitro and in vivo and approaches of targeting and tracing of stem cells in situ and in dynamic conditions in vivo;
4. Cellular and molecular mechanisms governing asymmetric division;
5. General characteristics and differentiation potential of mesenchymal stem cells;
6. Cellular and molecular mechanisms controlling differentiation of mesenchymal stem cells, incluyding the phenomenon of mechanotransduction;
7. Potential use of mesenchymal stem cells for bone and cartilage reconstruction;
8. Potential use of mesenchymal stem cells in the support of engraftment of hematopoietic stem cells;
9. Immunemodulating capabilities of mesenchymal stem cells, the cellular and molecular mechanisms underlying such activity;
10. Potential use of mesenchymal stem cells in control/alleviation of rejection phenomena upon organ transplantation, graft-versus-host disease (GVHD) and inflammations caused by viral and bacterial infection;
11. Potential use of mesenchymal stem cells as vehicles for targeted drug delivery: the case of anti-tumour approaches;
12. Characteristics and potential clinical application of neural stem cells in neurogenerative diseases;
13. Characteristics and potential clinical application of skin stem cells for the reconstitution of damaged skin;
14. Characteristics and potential clinical application of heart resident stem cells and circulating endothelial progenitor/stem cells exploited for the heart muscle repair;
15. Characteristics and potential clinical application of intestinal stem cells; organoids and innovative functional tracing technologies;
16. Characteristics and clinical use of hematopoietic stem cells: autologous and allogenic bone marrow and peripheral blood transplantation;
17. Characteristics and potential clinical application of embryonic stem cells;
18. Nuclear reprogramming and generation of iPS cells – induced Pluripotent Stem cells and future prospective of their use in the clinics.
Bibliography
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. An alternatively recommended textbook is "Functional Histology", 2nd edition by Jeffrey B. Kerr, published by Mobsy Elsevier Health Science. Because of the integrated nature of the Course, the inavailability of a more comprehensive text book, especially one exhaustively covering the biology of stem cells and their medical application potentials, it is absolutely mandatory for the students to attend the lectures. Other Course material is in the form of selected experimental and review articles published in the major scientific journals. The comprehensive list of these articles is provided separately.
Teaching methods
To reach the Course objective, translated into the effort to transmit to the student a comprehensive understanding of the morpho-functional characteristics of human tissues, how stem/progenitor cells contribute to these properties, and how these properties could be exploited to reconstitute tissues in disease conditions, the Course literature is based upon a selection of up-to-date text histology books and a selection of review and experimental milestone articles published in scientific journals of major impact. Landmarks discoveries are further extensively treated during the Lectures. Particular care is therefore taken to elaborate high quality illustrations as a support to the lecturers and make some of this material accessible to the students. Because of this unreplaceable contribution made by the Lecturer, afforded by his knowledge and scientific experience in the field, it is strongly recommended to the students to attend ALL lectures and to 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.
The Course benefits from an integrated contribution made by two younger Lecturers, Drs Mirca Lazzaretti and Domenica Mangieri, whose engagement in the Course is in its first part dedicated to morpho-functional description of the human tissues and the methods used to study them. These Lecturers also make a contribution to more interactive moments of the Course in which students are allowed to familiarize with the morphological characteristics of human tissues by viewing of representative histological samples. Finally, Drs Lazzaretti and Mangieri also are responsible for the elaboration of supplementary material in support of the first part of the Course.
Assessment methods and criteria
Attendance of the lectures is mandatory and students are called in to sign an attendance sheet for each lecture. For accessing written or oral examinations, it is required to have attended a minimum of 70% of the lectures. Students who of health- or family-reelated problems cannot attend any of the lectures should communicate their absence by email. Absence of work-related problems is also accepted and should similarly be communicated.
Course proficiency evaluation involves the delivery of a short Presentation on a causally assigned topic, selected among those thoroughly treated during the Course. The Presentation is judged for its quality in terms of clarity, accurateness and pertinence to the topic. Particular attention is given to the degree of knowledge of the student on the selected subject and how he/she articulates it. To select the topic to discuss, each student is called in individually toextract the topic from a list of 40 highly representative ones, which have been amply discussed during the Course. The Presentation should preferably not exceed 10 minutes and is followed by 5 minutes of questions related to the Presentation itself. These are posed with the intent to assess the student’s basic knowledge on the subject of the Course. If a Presentation is judged of insufficient quality andreceives a low score (vote), it is possible to make another one, in a different occasion and on a different subject, similarly sorted out by the student.
As a thumb rule, the Presentation should entail no more than 10-15 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 significant overview of the topic to be discussed.
Other information
The Course benefits from an integrated contribution made by two younger Lecturers, Drs Mirca Lazzaretti and Domenica Mangieri, whose role in the Course is to trreat in-depth the morpho-functional description of the human tissues and the methods used to study them. These Lecturers also make a contribution to more interactive moments of the Course in which students allowed to familiarize with the morphological characteristics of human tissues by viewing of representative histological samples. Finally, Drs Lazzaretti and Mangieri also are responsible for the elaboration of supplementary material in support of the first part of the Course.
2030 agenda goals for sustainable development
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