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Stem Cells & Neurological Disorders Said Ismail Faculty of Medicine University of Jordan

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Stem Cells & Neurological Disorders Said Ismail Faculty of Medicine University of Jordan

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  1. Stem Cells & Neurological Disorders Said Ismail Faculty of Medicine University of Jordan

  2. Outline: • Introduction • Types & Potency of Stem Cells • Embryonic Stem Cells • Adult Stem Cells • iPSCs • Tissue Engineering and Regenerative Medicine • Stem Cells & Neurological Disorders: • - Neural Stem Cells • - Examples of Therapeutic Applications • - Conclusion Stem Cells and Neurological Disorders

  3. Introduction Stem Cells and Neurological Disorders

  4. Benefits of stem cell research : • Treatment of complex diseases: • Chronic Disorders: Diabetes • Neurological Disorders: • Alzhimer’s • Parkinson’s • Spinal Cord Injuries • Heart disorders: MI • Regenerative medicine(Spare parts !) • Skin Cartilage • Bone Cornea • Heart Valves Stem Cells and Neurological Disorders

  5. Definition: • stem cells: • renew itself indefinitely • (ii) differentiate to multiple tissue types • A stem cell is not committed to • a specific function until it receives • a signal to differentiate into a • specialized cell Stem Cells and Neurological Disorders

  6. Types & Potency Stem Cells and Neurological Disorders

  7. Embryonic: • - Blastomere (4-5 day embryo) • - Pluripotent • Adult: • - Adult tissue • - multi or uni potent • Other : • - Fetal: • - Aborted embryos • - Pluripotent • - Umbilical: • - Umbilical cord blood • - Multipotent Stem Cells and Neurological Disorders

  8. Potency: 1.Totipotent (Fertilized egg) Generate: - all embryonic cells and tissues - supporting tissue like placenta and umbilical cord 2. Pluripotent - Give rise to cells of all 3 germ layers (ecto-, meso-, and endoderm - Come from embryos and fetal tissue - Have active telomerase (maintain long telomers) 3. Multipotent - Give rise to multiple different cell types 4. Unipotent - Cell differentiating along only one lineage Stem Cells and Neurological Disorders

  9. Stem Cells and Neurological Disorders

  10. Stem Cells and Neurological Disorders

  11. Stem Cells and Neurological Disorders

  12. Embryonic Stem Cell Stem Cells and Neurological Disorders

  13. The Embryonic Stem CellSource:1. IVF embryos2. Aborted Fetus3. Therapeutic cloning Stem Cells and Neurological Disorders

  14. IVF embryos Thousandsof frozen embryos are routinely destroyed when couples finish their treatment.

  15. Somatic Cell Nuclear Transfer The nucleus of a donated egg is removed and replaced with the nucleus of a mature, "somatic cell" (a skin cell, for example).

  16. Embryonic Stem Cell • First isolated and cultured in 1998 • From inner cell mass of blastocyst (4-5 day embryo). • Pluripotent with long-term self-renewal • Capable of unlimited number of divisions without differentiation • Can essentially live forever without forming tumors • Maintain normal diploid complement of chromosomes (stable karyotype) • Telomerase activity • Clonogenic: give rise to genetically identical group of cells • Expresses transcription factor Oct-4 (+ or – genes needed for proliferative state) • Spend most of their time in S phase • In-Vitro: 300 population doublings Stem Cells and Neurological Disorders

  17. Human Blastocyst showing Inner Cell Mass Stem Cells and Neurological Disorders

  18. GROWING HESC IN VITRO:

  19. Advantages: • Immortal: supply endless amount of cells • Flexible: can make any body cell • Available: IVF clinics • Disadvantages: • Hard to control their differentiation • Ethics • Immune rejection Stem Cells and Neurological Disorders

  20. Avoiding Immune rejection: • Genetically engineering stem cell to: • a. Express MHC antigens of recipient • b. produces stem cells with deleted MHC genes • 2. Therapeutic Cloning: • Clone somatic Cell nucleus of recipient into egg • develop into blastocyst and isolate ES cells • Such ES cells have recipient immunological profile • Co-transplantation with Hematopoitic Stem cells Stem Cells and Neurological Disorders

  21. Avoiding Immune rejection

  22. Laboratory tests to identify ESC : 1. Immortality: Sub-culturing stem cells for many months (long-term self-renewal) 2. Morphology: Inspecting culture by microscope (for undifferentiation) 3. Surface markers &Stemnss genes: (e.g. Oct-4) 4.Karyotype stability: Examining the state of chromosomes 5. Telomerase Activity 6. Pluripotency: testing differentiation potential into diff. cells types Stem Cells and Neurological Disorders

  23. Ethics and ESCs: Here Here or Here When is it OK….when is it NOT Stem Cells and Neurological Disorders

  24. Group of cells or Human life Stem Cells and Neurological Disorders

  25. Stem Cells and Neurological Disorders

  26. Adult Stem Cells Stem Cells and Neurological Disorders

  27. The Adult Stem Cell • Undifferentiated cell found in a specialized tissue in adult. • Capable of self-renewal • Become specialized to cell types of the tissue from which it originated. Properties: • Somatic • Long-term self-renewal • give rise to mature cell types • Generate intermediate cell (progenitors) “committed” • Can migrate whenever needed • Uni- or Multipotent Stem Cells and Neurological Disorders

  28. Sources of adult stem cells : • Bone marrow • Blood stream • Umbilical cord blood • Dental pulp of the tooth • Cornea and retina • Skeletal muscle • Liver • Skin (epithelia) • Gastrointestinal tract • Pancreas • Brain & spinal cord Stem Cells and Neurological Disorders

  29. Bone marrow Stem Cells and Neurological Disorders

  30. umbilical cord blood Stem Cells and Neurological Disorders

  31. Dental Pulp Stem Cells and Neurological Disorders

  32. Stem Cells and Neurological Disorders

  33. Adult stem cell plasticity • Plasticity: stem cell from one adult tissue can generate the differentiated cell types of another tissue: “unorthodox differentiation” or “transdifferentiation” • EX. Hematopoietic stem cell Neurons • Possible under specific conditions Stem Cells and Neurological Disorders

  34. Plasticity of adult stem cells Stem Cells and Neurological Disorders

  35. Advantages : • No immune rejection • Available: eg HSC • Partly specialized: easier to control differentiation • Flexible: under the right conditions Disadvantages : • Scarce (Rare): True for many Adult SCs • Unavailable: Some are difficult to isolate like Neural stem cells • Vanishing: Don’t live in culture as long as ES cells • Questionable quality: more prone to DNA abnormalities Stem Cells and Neurological Disorders

  36. Induced Pluripotent Stem Cells (iPSCs) Stem Cells and Neurological Disorders

  37. Induced Pluripotent Stem Cells (iPSCs):= Retro-differentiation = Re-programming • Producing stem cells from differentiated cells !!! • Pluripotent embryonic like stem cells are produced • Reversal of normal process • Does Not require human embryos • No donor…..No rejection • Less expensive • No Ethical issues Stem Cells and Neurological Disorders

  38. Main Key Genes: • iPSCs are derived from adult somatic cells by inducing expression • of certain Stemnessgenes: (usually by viral vectors: risk !!!) • - eg: Master transcriptional regulators: • Oct-4 • Sox2 • Nonog • - other genes: c-Myc (oncogene: cancer risk !!!!) Stem Cells and Neurological Disorders

  39. Pluripotency: Believed to be identical to embryonic stem (ES) cells in many respects: - expression of certain stemness genes - chromatin methylation patterns - doubling time - embryoid body formation - teratoma formation - viable chimera formation - potency and differentiability Stem Cells and Neurological Disorders

  40. Generation of induced pluripotent stem (iPS) cells • Isolate and culture donor cells. • (2) Transfect stemness genes into cells by viral vectors. Red cells express those genes • (3) Harvest and culture the cells according to ES cell culture, on feeder cells (light gray) • (4) A subset of the transfected cells become iPS cells and generate ES-like colonies Stem Cells and Neurological Disorders

  41. Neurogenesis of iPSPluripotent Neuronal Stem Cells derived from Adult Leukocytes

  42. Potential target disorders for Stem Cell Therapy: • Leukemia • Heart damage • Anemia • Cornea damage • Retinal damage • Parkinson’s • Alzhimer’s • Diabetes • Spinal Cord Injury • Kidney Failure • Skin grafts Stem Cells and Neurological Disorders

  43. leukemia Stem Cells and Neurological Disorders

  44. Heart damage Stem Cells and Neurological Disorders

  45. Diabetes Stem Cells and Neurological Disorders

  46. Tissue Engineering & Regenerative Medicine Stem Cells and Neurological Disorders

  47. Bone Repair Stem Cells and Neurological Disorders

  48. Skin graft grown from stem cells Stem Cells and Neurological Disorders

  49. Cornea Stem Cells and Neurological Disorders