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).
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, immunology, genetics and biomedicine and have previously been confronted with all primary laboratory techniques within the field of 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 while in the body (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.
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.
The Couse then touches upon the phenomenon of cell fusion and how this may affect the biological behaviour of stem cells and the understanding of the biological-functional traits of neural stem cells and how the fetal ones could be employed in regenerative medicine. 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.
Topics of the entire ITUBACCS Course for the total of 9 CFU are as follows:
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 muscles and their 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 unique morpho-functional organization of the Central (CNS) and Peripheral (PNS) Nervous Systems and the phenomenon of axon regrowth.
7. The concepts of “stemness”, asymmetric division, self-renewal and multipotency from a molecular standpoint.
8. The procedures and limitations in the in vivo tracing of stem cells and their progenies after transplantation.
9. The characteristics of the prototype stem cell – the hematopoietic stem cell and its clinical use.
10. The cellular and molecular mechanisms controlling stromal/mesenchymal stem cells and their clinical exploitation potential.
11. The cellular and molecular mechanisms controlling neural stem cells and their clinical exploitation potential.
12. The identification and characteristics of cardiac stem cells and vascular progenitor cells.
13. 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 "Functional Histology", 2nd edition by Jeffrey B. Kerr, published by Mobsy Elsevier Health Science. An alternatively recommended textbook is "Histology: A Text and Atlas", by Micheal H. Ross and Wojciech Pawlina, published by Lippincott Williams & Wilkins. 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 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 major impact scientific journals. 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.
Evaluation of the students is uniquely based upon a combined written exam for the first part of the Course and a 10-15 minutes-long oral presentation to be given by the students to the Lecturer. The subject of the presentation is sorted out by the student and is tightly connected to the topic and content of the Course. On the other hand, compilation and elaboration of the presentation is entirely at discretion of the student who is encouraged to make use of proper illustrations to discuss the selected topic. It is strongly required that the presentation should highlight that the student is well familiar with the basic concepts of stem cell biology and the application potential of these cells and has acquired a full understanding of how this subject could be studied.
Assessment methods and criteria
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.
The Course benefits from an integrated contribution made by two younger Lecturers, Drs Mirca Lazzaretti and Domenica Mangieri, who address specific issues in the first part of the Course 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 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.