STEM CELLS

1. STEM CELLS IIS LS PICCOLO CAPO D’ORLANDO

2. STEM CELLS CLASSIFICATION STORAGE ETHICS DEBATE RESEARCH & EXPERIMENTS CONSIDERATIONS

3. In all forms of multicellular life, tissue regeneration is a physiological process. Such renewal is ensured by the stem cells, which are responsible for maintaining the integrity of tissue and the continuous supply of new cells. Stemcells in culture Musclecells Intestinalcells Livercells Blood cells Nervouscells Cardiaccells WHAT IS THEIR ROLE IN THE HUMAN ORGANISM?

5. They are primitive cells, non-specialized, able to differentiate in approximately 200 different cell types that make up our body. Neurons, skin cells, muscle cells, bone cells, liver cells and so on.

6. What am Igoing to do when Igrow up? Wich genes should Iactivate? • We can compare the stem cell to a baby cell that has not decided yetwhat to do when it grows up.Once it has decided what to do and then the role it will play in the body, the stem cell specializes through a process called differentiation.

7. During differentiation, certain genes are expressed and are responsible for their specific functions, others are suppressed. Therefore, the cells of an organism belonging to different tissues, contain the same genotype but differ in their phenotype. DIFFERENTIAL GENE EXPRESSION

8. By symmetric replication (bivalent mitosis), the stem cell gives rive to two daughter cells: • - one will be identical to the mother ( still stem cell), in this way maintaining the tissue’s stamina pool. • - one will be different, called committed progenitor of a population of cells which will continue differentiating. Stemcell Stemcell «destined» Progenitor Precursor Somaticcell Symmetric replication

9. With the asymmetrical replication the stem cell gives rise to two identical daughter cells which can both be either stem cells or two progenitor cells ASYMMETRIC REPLICATION

10. In order to be called a stem cel, it must have these features: :  - self-renewal or the ability to replicate an indefinite number of times. - power: the possibility to originate one or more cell types. …. Replicate itself A single stemcell can.. Differentiateintodifferentcelltypes FEATURES OF STEM CELLS

11. Based on their different ability stem cells are distinguished in: • TOTIPOTENT • OLIGOPOTENT • PLURIPOTENT • MULTIPOTENT • UNIPOTENT STAMINA’S POWER

12. Are able to give rise to all the differentiated cells of an organism, including the extra-embryonictissues, as placenta and yolk sac. In mammals the only totipotent cell is the zygote, which can be defined as such until the blastomere stage (8 cells stage) 12-15 hours afterfertilization 2-3 daysafterfertilization TOTIPOTENT STEM CELLS Fertlization and formation of the zygote 2-cells stage 4-cells stage 8-cells stage

13. Being totipotent cells, if separated among each others, blastomers can give rise to a complete individual. 8 separatedblastomers What does totipotency imply?

14. Once the 8 cells stage has finished, the zygote keeps dividing by mitosis and a morula is formed (16 cells stage). • Morula’s cells are not totipotent. • Around one week following the fecundation, blastocyststage is reached. 1 week afterfertilization 5-6 daysafterfertilization Trophoblast What does happen during the development? Node or embryonicbutton Morula (aslowas 16 cells) Blastocyst (about 120 cells)

15. Oligopotent cell lines have the ability to transform into quite a limited number of several other types of cells an example of which is a myeloid cells, B cells, T cells, plasma cells or the cells comprising the lymphoid system. • An example of oligopotent cells are myeloid cell which can differentiate into any of the blood stem cells found in lymphatic • Oligopotentcells are known to be less potent compared to multipotent, pluripotent or totipotent cells but in the case of unipotentcells, they are found to be more potent. • The corneal epithelium is a squamous epithelium that is constantly renewing and is Oligopotent. OLIGOPOTENT STEM CELLS

16. Blastocysts are pluripotent cells. • This means they can neither form an entire individual nor extra-embryonictissues. • However, pluripotent stem cells can give rise to every type of cell: our bodycells, neurons, blood cells, etc. Blastocysts Blood cells Hepathocytes Neurons Cardiomyocythes PLURIPOTENT STEM CELLS

17. Multipotent stem cells can give rise only to a single cellular lineage. Hematopoietic stem cells are multipotent stem cells able to differentiate in any figurative element of the blood, but unable to form neither muscle cells nor nerve cells. Hemopoietic multipotent stem cells

18. Being multipotent cells, neuronal stem cells are only able to give rise to cells concerning nervous tissue: • neurons • astrocytes • oligodendrocytes Natural stemcell Natural progenitor Oligodendrocytic Precursor Astrocyte Precursor Neuronal precursor Neuronal multipotent stem cells oligodendrocytes Astrocytes Neuron

19. Unipotent stem cells are able to differentiate only to one type of cells and, for this reason, they are also named “precursor cells”. • They retain the ability of self-renewing: they can replicate countless times in order to repair a tissue. • An example of unipotent stem cells are the Hepatocytes Unipotent Stem cells

20. According to their origin, we can classify stem cells into: • Embryonal Stem Cells • Umbilical cord or placental blood stem cells • Adult (somatic) stem cells Stem Cells’ Origin

21. Embryonic stem cells are taken from blastocysts, 4-5 days after the fecundation process before the implantation into the uterus. The blastocyst is made up of three structures:trophoblast, the external cellular layer surrounding the blastocoele, that cavity in which the blastocyst is located and, at the extremity, a group of cells (inner mass cells). Trophoblast Inner mass cell Blastocysts after 6 days Pluripotent embryonic Stem Cells (ES cells)

22. From the inner cell mass Embryonal stem cells are collected They can be used to cure many diseases such as: Parkinson’s disease Diseases of the retina https://www.youtube.com/watch?v=ewEdR5_V-v0 (BBC treatment for blindness) Specimen and cell Culture

23. Fetal stem cells are obtained from spontaneous abortion while those from the umbilical and placental blood are collected after delivery (childbirth) and are used for hematologic transplantation. In 2006 even the Catholic Church took an official position acknowledging the scientific validity of cordonal stem cells’ use. Fetal Stem cells - from the umbilical cord and from placental blood

24. They provide for the maintenance and repair of the tissue in which they are located: brain, eyes, gonads, dental pulp, breast, bone marrow, retina, intestine (bowel), skin and amniotic fluid. • The most studied are those of the bone marrow which can be distinguished into hematopoietic and mesenchymal (the latest can differentiate into many cellular types) Adult Stem Cells (ASCs)

25. Concerning the medical field, Stem cells could be used for many purposes but, with exception of those therapy based on hematopoietic stem cells, at the moment, in the clinical practice no other treatment is based on these cells (only some animal trials) However, adult stem cells have been clinically tested and can give us a huge hope concerning the possibility of future therapy regarding: • degenerative diseases of the nervous system ( Parkinson’s disease, Alzheimer’s disease, multiple sclerosis) • reconstruction of the spinal cord damaged by physical trauma. • musculo-skeletal diseases • cardiac tissue reconstruction (following an infarct) Application in medical field

26. Embryonal stem cells specimen necessarily requires embryonal destruction. Therefore it’s lawful to ask ourself : is it morally acceptable to kill an human embryo, although it is for beneficial purposes? This question is the object of a religious and philosophic dispute, which is splitting not only the public opinion but also religious, politicians, doctors and researchers. The real question is : is the embryo already a life or still “a thing”? Ethical debate regarding the utilization of embryonal stem cells

27. REASON TO SAY YES • The embryo is not yet an individual • It is available “biological Material” • which can be use to improve knowledges and experimentations • Thanks to the acquired knowledge it would be possible to treat untreatable diseases (Alzheimer, Parkinson, dystrophies, etc) • REASON TO SAY NO • The Embryo already is an human being • “It” has the right of life, it is not “available material” although it can be used for advancement of knowledges • ESC sample requires the embryo’s death, therefore it is unacceptable. • a knowledge improvement could be reached alto throw experiments on adult stem cells Reason to say either YES or NOT

28. A particular case concerns Italy. • according to the italian law it is allowed the utilization on already derived lineages which can be exchanged and imported in case of collaboration between different countries but the funding to allow researches is denied. • The Italian law doesnotallowto makeexperiments on embryos and human clonation (therapeutic and reproductive) • We can differentiate 3 different types • Stem cells donated by adult individuals (in the case of juvenile age it’s fundamental to have the parentalconsense) • stem cells taken from “waste tissues”, such as in the case of the umbilical cord;in this case itis mandatory to have the parent’s authorization. • In the case of abortion the mother can give her consensus regarding the donation of “abortion material” WhataboutItaly?

29. A long-running controversy sparked by the Italian government’s decision to fund a clinical trial of an unapproved stem cell therapy may have reached its final chapter. Last week, a panel of experts appointed by the Italian Ministry of Health concluded that the trial of the so-called Stamina method should not move forward. • Meanwhile, 20 people involved in promoting the therapy, including its leading proponent, are facing allegations of criminal conduct. • The controversy stretches back to 2006, when the Stamina Foundation, a private organization based in Turin, began promoting the stem cell treatment, which has not been approved by Italian regulators. Foundation President DavideVannoni claims that the therapy, based on bone marrow stem cells, can promote the growth of new neurons and hence cure a vast range of neurodegenerative diseases. In 2013, the Italian Parliament earmarked €3 million for a trial, amid pressure from patients and some media outlets, and despite investigations by health care officials that resulted in decrees to halt the treatments. The decision to fund the trial drew immediate criticism from stem cell researchers and others, prompting officials to order the initial 2013 expert review.

30. Vannoni says he will again go to court in an effort to set aside the panel’s conclusions. • No patients are currently receiving the Stamina treatment, in part because prosecutors in Turin recently seized vials containing patient cells and tissues from a hospital involved in the therapy. • Luca Pani, director of Italy’s drug regulator, AIFA, says his agency’s investigations show that the treatments should not resume. Investigators found “a number of serious violations which leave no room for interpretation,” he said in a statement issued after the panel issued its recommendation. Different positions

31. Because of the inefficency of the Italian law manychildrenare forced to search for a treatment in othercountrieswhenstemcells are theironlyhope. • A clearexampleisrepresented by a 8 yearsold girl from a small village in Sicily: Federica. • Shehasbeendiagnosed with a congenitaldisease (SMARD1) manifested in the case in whichbothparents are carriers of a mutation on chromosome 11. *The cute Federica The case of “La dolce Federica” *

32. This abnormality causes a progressive paralysis affecting the muscles of the body till the involvement of the diaphragm, impairing respiration, deglutition and all the vital activities. • Her parents found out that a treatment with stem cells is possible and could change their daughter’s life but due to the obstinacy of the Italian government they must go to Israel.

33. Taking into account the actual position of the Italian government on this very important and hot topic: • -what would you propose as a possible solution to solve this problem? • - Is it fair to force somebody to leave his/her country to seek for a treatment in order to live? Considerations