1. Jasna Marinović, M.D., Ph.D. Associate Professor Department of Physiology

2. Key Concepts What are stem cells? What are different types of stem cells and where do they come from? What is the potential for new medical treatments using stem cells?

3. What are stem cells? unspecialized cells capable of renewing themselves through cell division. But, under certain conditions, stem cells can be induced to differentiate into another, tissuse- or organ- specific cell type.

4. Embryonic development

5. Historic perspective

7. Blastocyst

8. Germ layers

9. Differentiation is gradual

10. As differentiation reaches its end, the stem cells become very sparse

11. Body renewal - maintenance

12. Stem cells

13. Hematopoetic stem cells

15. Types of stem cells

16. Embrionic stem (ES) cells

17. ES cells can differentiate into any tissue

18. Human embryonic stem cells

19. Adult stem cells

20. Embyonic Adult Most potential Can form all cell types Immortal in culture Plentiful Organ-specific Can form few cell types Limited life-span (in culture) Hard to isolate

21. Adult stem cells First identified only in bone marrow (hematopoetic - producing blood elements; and stromal stem cells – producing bone, cartilage, fat). In 1990s, identified in heart, brain, blood vessels, skeletal muscle, gut, liver, ovaries, testis. Very sparse, quiescent and activated only after injury. Insufficient to enable organ regeneration.

22. Induced Pluripotent Stem Cells “genetically reprogrammed adult cells to assume embryonic stem-cell phenotype - dedifferentiation” Generated in 2006. Viruses used to introduce reprogramming-genes into adult cells Limitation: danger from metastatic cancer

23. (Potential)Applications of Stem cells 1. Testing new medications on differentiated cells from human pluripotent stem cell lines 2. Cell-based therapies Source of replacement cells for repair of terminally damaged tissues (nerve cells, heart cells…) 3. Tissue and organ engineering “in vitro”

24. Use of stem cells in heart disease  Cardiac transplant currently the only therapy for advanced heart failure – too few donor hearts.  Cardiomyocytes proliferation after birth extremely rare – turnover rate 1 % /year (young adults).  First studies in mice transplanted with skeletal myoblasts were promising  human trials

25. Milestones in clinical trials of cardiac regeneration therapies (Lancet 2012;379:933-42)

26. Lancet 2012;379:933-42

27. Engineering whole organs and complex tissues  Ultimate goal, replacing the need for donor organs (insufficient).  Necessary:  Biological scaffold of extracellular matrix (template for tissue reconstruction)  Appropriate autologous stem cells or differentiated cells  Successful examples in humans:  trachea, oesophagus, skeletal muscle

28. Engineered airway “Clinical transplantation of a tissue-engineered airway” Lancet 2008; 372; 2023-30.