Human Histology and Biology and Clinical Applications of Stem Cells.
Learning outcomes of the course unit
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 charcateristics 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 properties have been 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.
Effective following of the second part of the course requires a solid background knowledge in cell biology and basic knowledge about developmental biology. The student also needs to be highly familiar with principles of biochemistry, molecular biology, immunology/virology, general pathology and genetics, and have previously been confronted with all primary laboratory techniques within the fields of biomedicine and life sciences.
Course contents summary
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 in their natural environment (techniques for Whole-body imaging). In particular it 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 how this may impact on the homeostatsis of that tissue.
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 nomenclature currently adopted 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 to 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 te 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 the "Nobel prize-winning" topic of iPS cells - induced Pluripotent Stem cells - and how this relates to nuclear reprogramming originally documented in Xenopus by Sir John B. Gurdon. A certain amount of time is also dedicated to the milestone discoveries of Rudolph Jaenish and the observations made by the Nobel Laureate Sir Martin Evans on teratomas. Lectures of this last part of the Course exhaustively detail the original work of Shinya Yamanaka and how these findings were followed-up by the entire scientific community interested in understanding the biology of stem cells, such as to translate this knowledge into clinical applications. Thus, particular emphasis is given to the application potential of iPS cells, their prospectives and their applicative limitations.
The comprehensive programme of the Course ITUBACCS entails the following subjects:
1. Methods, instruments and approaches for the analysis of tissue structure and composition;
2. Structural diversity and regeneration capability of epithelial tissues and the skin model of wound-healing;
3. Structural-functional traits of skeletal and cardiac muscle tissues and their intrinsic regenerative potentials;
4. The hematopoietic system: its morpho-functional features, its stem/progenitor cells, its reconstitution pattern and the process of lymphocyte recycling;
5. The characteristics of vascular structures, the process of angiogenesis, and the nature and traits of multipotent perivascular cells;
6. The concepts of “stemness”, asymmetric division, self-renewal and multipotency from a molecular stand point;
7. The procedures and limitations in the in vivo tracing of stem cells and their progenies after transplantation;
8. The characteristics of the prototype stem cell – the hematopoietic stem cell and its clinical use;
9. The cellular and molecular mechanisms controlling stromal/mesenchymal stem cells and their clinical exploitation potential;
10. The cellular and molecular mechanisms controlling neural stem cells and their clinical exploitation potential;
11. The identification and characteristics of cardiac stem cells and vascular progenitor cells;
12. The potential of embryonic stem cells, epigenetics of stem cells and the “birth” and exploitation potential of iPS cells (“induced Pluripotent Stem cells).
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 alternative recommended text book is "Functional Histology", 2nd edition by Jeffrey B. Kerr, published by Mobsy Elsevier Health Science.
These text books are complemented by a "Compendium", originally elaborated by Drs Mirca Lazzaretti and Domenica Mangieri and considered to be of particular utility for a comprehensive overview of the course's content. The "Compendium" is available through Libreria Santa Croce (Parma).
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.
To reach the Course objective, meaning 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 they could be exploited to reconstitute them 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 by the Lectures. Particular care is therefore taken to elaborate high quality illutsrations 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 and afforded by his knowledge and scientific experience in the field, it is strongly recommended to the studnets 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.
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-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 to the Lecturer.
Course proficiency evaluation involves the combined evaluation of a written exam for the Course module related to "Histology" and an oral presentation for the Course module related to the "Biology of stem cell". The score obtained for this latter presentation weights more than former for the assignment of the final score, consistently with the different amounts of CFUs for each of the subjects of the Course. The written exam for the "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 are not reached. The test cannot be repeated if the score obtained is equal to or above 18 points. The examination of the part related to "stem cells" requires the delivery of a short Presentation on a causally assigned topic, selected by the student himself/herself among a selection of pertinent topics, i.e. the topic will be extracted by each student individually from a list of 40 highly representative of topics amply discussed during the Course. 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 preferably not exceed 10 minutes and is followed by 5 minutes of discussion related to the Presentation itself, 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, 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 sufficiently clear Comprehensive view on the treatred subject will similarly be judged negatively.
The Course 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.