Current Perspectives on Stem Cell Biology

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Koç Medicine Phase i Lecture Dec 24, 2010

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  • Beautiful presentation... really innovative and amazingly done... kindly mail me at drabykbabu@gmail.com
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  • kindly send your presentation sir,i am student it's truly for study purposes my email:drsandeepakh@gmail.com
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  • As previous readers, I applose your presentation. I would appreciate if you would send me presentation too. I am preparing education for biospychology for I year psychology students. It would be very helpfull. Thanks. lolita.rapoliene@inbox.lt
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  • sir really great ppt for educational purpose can you please send me this ppt on my mail ahmedsavanikgn@gmail.com . as i found unable to download this on this site . thank u
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  • The stem cells have been traditionally divided into two categories, the totipotent ones, which are capable to differentiate into all three germ layers and since a few years ago this property was thought to be confined to embryonic cells and secondly the multipotent stem cells whose progeny is in fact limited to one germ line
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  • Actually physiological – evidence? – CAN isolate them from circulating blood; and lots of bmtx pm studies, eg….
  • Current Perspectives on Stem Cell Biology

    1. 1. CURRENT PERSPECTIVES ON STEM CELL BIOLOGY AND FUTURE IMPLICATIONS Emin Kansu,MD,FACP [email_address] Hacettepe University Institute of Oncology
    2. 2. 1953
    3. 3. NATURE February 15,2001 HUMAN GENOME MAP
    4. 4. CLONING TECHNOLOGY
    5. 5. DOLLY First Cloned Animal- 19*****
    6. 8. <ul><li>REGENERATIVE MEDICINE and THE FUTURE .. </li></ul>PRESENTATION <ul><li>STEM CELL PLURIPOTENCY </li></ul><ul><li>STEM CELL HOMING and “NICHE” </li></ul><ul><li>DEFINITION OF STEM CELLS </li></ul><ul><li>STEM CELL ONTOGENY AND HEMATOPOIETIC STEM CELL (HSC) </li></ul><ul><li> </li></ul><ul><li>STEM CELL TYPES </li></ul>
    7. 9. HIROSHIMA ve NAGASAKI August 1945 A-BOMB
    8. 10. BALB/c BONE MARROW CELLS MOUSE SPLEEN IRRADIATED MOUSE BONE MARROW BALB/c BALB/c IRRADIATION WILL EMPTY BONE MARROW SPACE AND RECONSTITUTION CAN BE ACHIEVED BY NEW STEM CELLS CFU-S INFUSION OF IRRADIATION
    9. 12. FROM EMBRYONIC STEM CELLS TO A NEWBORN Human Embryonic Stem Cells (hESC)
    10. 13. STEM CELL <ul><li>PRIMITIVE CELL WITH A VERY HIGH POTENTIAL AND INFINITE ABILITY OF </li></ul><ul><li>SELF-RENEWAL AND DIFFERENTIATION </li></ul><ul><li>INTO OTHER CELL TYPES </li></ul>
    11. 14. STEM CELLS <ul><li>SELF-RENEWAL CAPACITY </li></ul><ul><li>PLURIPOTENCY </li></ul><ul><li>CLONALITY </li></ul><ul><li>DIFFERENTIATION ABILITY </li></ul>
    12. 15. STEM CELLS <ul><li>UNLIMITED POTENTIAL FOR SELF-RENEWAL </li></ul><ul><li>(* TO KEEP THE STEM CELL NUMBERS AND POOL SIZE CONSTANT) </li></ul><ul><li>MULTIPOTENT and CLONAL </li></ul><ul><li>MULTILINEAGE DIFFERENTIATION </li></ul><ul><li>ABILITY TO ENGRAFT TO ANOTHER HOST WITH </li></ul><ul><li>COMPLETE RE-POPULATION </li></ul>
    13. 16. STEM CELL STEM CELL SYMMETRIC STEM CELL DIVISION STEM CELL
    14. 17. STEM CELL DIFFERENTIATED CELL STEM CELL ASYMMETRIC STEM CELL DIVISION
    15. 18. STEM CELL SELF-RENEWAL STEM CELL DIFFERENTIATION DIFFERENTIATED CELL (e.g.Myocyte, Neuron)
    16. 19. STEM CELLS I.Weissmann’05 DIFFERENTIATION SELF-RENEWAL MITOSIS APOPTOSIS G 1 Damar MIGRATION MOBILIZATION > 30.000/DAY (1-5 mins))
    17. 20. SPERM + OVUM DEVELOPMENT OF EMBRYO AND NEWBORN FERTILIZATION ESC BLASTOCYTE
    18. 21. EMBRYONIC STEM CELLS ECTODERM MESODERM ENDODERM TISSUE SPECIFIC ADULT STEM CELLS DIFFERENTIATED MATURE CELLS
    19. 22. <ul><li>EMBRYONIC STEM CELLS (ESC) </li></ul><ul><li> SOMATIC GERM </li></ul><ul><li> STEM CELLS STEM CELLS </li></ul><ul><li>ENDODERM ECTODERM NEURAL CREST MESODERM GAMETS </li></ul>
    20. 23. <ul><li>SOMATIC STEM CELLS </li></ul><ul><li>ENDODERM ECTODERM NEURAL CREST MESODERM </li></ul><ul><li>Liver Skin Nerves Blood </li></ul><ul><li>Gut Hair Pigmented Cells Muscle </li></ul><ul><li>Pancreas Bone </li></ul><ul><li> Cartilage </li></ul>
    21. 25. STEM CELLS <ul><li>TOTIPOTENT </li></ul><ul><li>PLURIPOTENT </li></ul><ul><li>UNIPOTENT </li></ul>
    22. 26. STEM CELLS <ul><li>TOTIPOTENT : capable of differentiating into all three germ layers: E ndoderm, E ctoderm and M esoderm = EMBRYONIC STEM CELL </li></ul><ul><li>PLURIPOTENT : whose progeny is limited to one germ layer = MESODERMAL STEM CELL </li></ul>
    23. 29. HOW THEY ARE TRAINED FOR SELF-RENEWAL AND PLURIPOTENCY ?
    24. 30. SITES OF HEMATOPOIETIC STEM CELLS YOLK SAC AGM FETAL LIVER BONE MARROW PRIMITIVE ERYTROPOEISIS PLACENTA
    25. 31. HEMATOPOIETIC STEM CELLS PLURIPOTENT STEM CELL MESODERM Hemangioblast HEMO ENDODERM HSC EMBRYO 7.5 DAYS 10.5 12.5 15.5 BIRTH PRIMITIVE STREAK YOLK SAC PLACENTA FETAL LIVER BONE MARROW MICROENVIRONMENT DEVELOPMENT OF HEMATOPOIETIC STEM CELL
    26. 32. G O RESTING “ Dormant” STEM CELL DIFFERENTIATION SENESCENCE SPECIFICATION CELL CYCLE APOPTOSIS G 1 G 0 M HEMATOPOIETIC STEM CELL POOL
    27. 33. DEVELOPMENT OF STEM CELL “ NICHE” YOLK SAC PLACENTA FETAL LIVER BONE MARROW NICHE : ENDOTHELIAL CELLS OSTEOBLASTS Trabecular Bone
    28. 34. STEM CELLS PROGENITORS DIFFERENTIATED MATURE CELLS
    29. 35. STEM CELLS PROGENITORS DIFFERENTIATED CELLS Decline in Replication Potential Increasing Degree of Differentiation STEM CELL DIFFERENTIATION
    30. 36. SELF-RENEWAL Self-Renewal : no Mitotic activity : ++ *** Self-Renewal :no Mitosis : no SC PC DC
    31. 37. HEMATOPOIETIC STEM CELLS (HSC)
    32. 38. HEMATOPOIETIC STEM CELLS RED CELLS MONOCYTES PLATELETS LYMPHOCYTES EOSINOPHILS NEUTROPHILS BASOPHILS
    33. 39. THYMUS BONE MARROW HEMATOPOETIC STEM CELL
    34. 40. BONE MARROW UNIVERSITY (State)
    35. 41. THYMUS UNIVERSITY PROLIFERATION DELETION SELECTION T-LYMPHOCYTE FACULTY
    36. 42. MICROANATOMY OF BONE MARROW
    37. 43. BONE MARROW UNIVERSITY – INTERNAL STRUCTURES Central Sinus
    38. 44. BONE MARROW : “ UNIVERSITY CAMPUS” SINUS Adventitial cell My ERYT ( Mesodermal Stem Cell) CELLS
    39. 45. Stem Cell Education Site = NICHE 1978
    40. 46. HEMATOPOIETIC STEM CELLS “ NICHE” “ Education Sites for Stem Cells”
    41. 47. BONE MARROW “NICHE ” SINUS Adventitial cell My ERYT ( Mesodermal Stem Cell) CELLS NICHE
    42. 48. “ EDUCATION ” OF HEMATOPOIETIC STEM CELLS AT “NICHE” SITE “ NICHE” MHC HEMATOPOIETIC STEM CELL DC CD4+ T- Cells CD8+ T- CElls NK Cells NKT Cells TReg
    43. 49. STEM CELL AT THE “ NICHE ” STEM CELL Myeloblast BONE MARROW STROMA “ NICHE” MYELOID CELLS
    44. 50. SELF-RENEWAL CAPACITY LT-HSC ST-HSC MPP NK+ Cell T Cell B Cell GIMP MEP PMN MEG PLTS RBC CLP CMP
    45. 51. HEMATOPOIETIC STEM CELLS-MOUSE LT-HSC ST-HSC Progenitors I.Weissman’05 Common Lymphoid Common Myeloid
    46. 53. HEMATOPOIETIC STEM CELLS RED CELLS MONOCYTES PLATELETS LYMPHOCYTES EOSINOPHILS NEUTROPHILS BASOPHILS
    47. 54. PLURIPOTENCY GENES IN STEM CELLS <ul><li>Oct – 4 </li></ul><ul><li>Nanog </li></ul><ul><li>Sox 2 </li></ul>
    48. 55. OCT 4 NANOG SOX 2 DEVELOPMENTAL REGULATORS PROGRAMMING DIFFERENTIATION
    49. 56. STEM CELLS <ul><li>HOW WE CAN IDENTIFY ? </li></ul>
    50. 57. PERIPHERAL BLOOD LYMPHOCYTES Stem Cell ?
    51. 58. <ul><li>IDENTIFYING STEM CELLS </li></ul>BFU-E ERYTHROID STEM CELL COLONY FORMING UNITS PERIPHERAL BLOOD IN VITRO Cultures
    52. 59. STEM CELL MARKERS : MOUSE vs HUMAN c-kit + Thy1 low sca-1 + c-kit + Thy1 low CD34 + NEGATIVE B 220 Mac-1 Gr-1 CD3 CD4 CD8 Ter 119 NEGATIVE CD38 CD10 CD14 CD15 CD16 CD19 CD20 I.Weissman
    53. 60. STEM CELLS……
    54. 61. STEM CELL TYPES <ul><li>ADULT (ASC) </li></ul><ul><li>EMBRYONIC (ESC) </li></ul><ul><li>MESENCHYMAL (MSC) </li></ul><ul><li>CORD BLOOD (CBSC) </li></ul><ul><li>INDUCIBLE PLURIPOTENT (iPS) </li></ul>
    55. 62. STEM CELL TYPES <ul><li>ADULT </li></ul><ul><li>MESODERMAL </li></ul><ul><li>EMBRYONIC </li></ul><ul><li>CORD BLOOD </li></ul>
    56. 63. ADULT STEM CELLS <ul><li>Terms Used : ADULT STEM CELLS (ASCs) </li></ul><ul><li>SOMATIC STEM CELLS </li></ul><ul><li>TISSUE STEM CELLS </li></ul><ul><li>POST-NATAL STEM CELLS </li></ul><ul><li>ASCs HAVE BEEN ISOLATED FROM NUMEROUS ADULT TISSUES - UMBLICAL CORD – PLACENTA </li></ul>
    57. 64. adapted from : Korbling & Estrov, NEJM 2003 ADULT STEM CELLS
    58. 65. ADULT STEM CELLS <ul><li>BONE MARROW STEM CELLS**(HSC) </li></ul><ul><li>PERIPHERAL BLOOD STEM CELLS </li></ul><ul><li>NEURONAL STEM CELLS </li></ul><ul><li>MUSCLE STEM CELLS (SATELLITE CELLS) </li></ul><ul><li>LIVER STEM CELLS </li></ul><ul><li>PANCREATIC STEM CELLS </li></ul><ul><li>CORNEAL LIMBAL STEM CELLS </li></ul><ul><li>MAMMARY STEM CELLS </li></ul><ul><li>SALIVARY GLAND STEM CELLS </li></ul><ul><li>SKIN STEM CELLS </li></ul><ul><li>CARTILAGE STEM CELLS </li></ul><ul><li>ADIPOSE DERIVED STEM CELLS </li></ul><ul><li>UMBLICAL CORD BLOOD CELLS </li></ul><ul><li>UMBLICAL CORD MESENCHYME CELLS </li></ul><ul><li>AMNIOTIC STEM CELLS </li></ul><ul><li>PARATHYROID GLAND STEM CELLS </li></ul>
    59. 66. HEMATOPOIETIC STEM CELLS RED CELLS MONOCYTES PLATELETS LYMPHOCYTES EOSINOPHILS NEUTROPHILS BASOPHILS
    60. 67. ALLOGENEIC STEM CELL TRANSPLANTATION RECIPIENT HEALTHY PERSON HEMATOPOIETIC STEM CELLS
    61. 68. ANNUAL NUMBERS OF BLOOD AND MARROW TRANSPLANTS WORLDWIDE 1970-2000 MDM01_21.ppt NUMBER OF TRANSPLANTS YEAR 1970 1975 1980 1985 1990 1995 Autologous Allogeneic 2000 0 5,000 10,000 15,000 20,000 25,000 30,000 35,000 40,000
    62. 69. E.DONNALL THOMAS, M.D. Emeritus Professor of Medicine University of Washington Fred Hutchinson Cancer Research Center - Seattle, USA Nobel Laureate for his contributions to Hematopoietic Stem Cell Transplantation in hematologic disorders 1990 1990
    63. 70. STEM CELL TYPES <ul><li>ADULT (ASC)** </li></ul><ul><li>EMBRYONIC (ESC) </li></ul><ul><li>MESENCHYMAL (MSC) </li></ul><ul><li>CORD BLOOD (CBSC) </li></ul>
    64. 71. Morphology of Mesodermal Progenitor Cells (MSC) (CD 45- GlyA-)
    65. 72. MESENCHYMAL STEM CELLS BONE CARTILAGE MUSCLE TENDON LIGAMENT CONNECTIVE TISSUE Chondroblasts Collagen II SM Myoblast Sm Myosin CaPo4 Osteoblasts
    66. 73. STEM CELL TYPES <ul><li>ADULT (ASC)** </li></ul><ul><li>EMBRYONIC (ESC) </li></ul><ul><li>MESENCHYMAL (MSC) </li></ul><ul><li>CORD BLOOD (CBSC) </li></ul>
    67. 74. FROM EMBRYONIC STEM CELLS TO A NEWBORN Human Embryonic Stem Cells (hESC)
    68. 75. Sir MARTIN EVANS University of Cardiff U.K.
    69. 76. MOUSE EMBRYONIC STEM CELLS Martin Evans’71 & 81
    70. 77. 2007 Physiology and Medicine Oliver Smithies Univ North Carolina U.S.A. Mario Capecchi Univ of Utah U.S.A. Sir Martin Evans Cardiff Univ U.K. “ Contributions to Embryonic Stem Cell Biology and Development of Knock-Out Mouse Model to Understand Pathobiology of Diseases”
    71. 79. SPERM + OVUM DEVELOPMENT OF EMBRYO AND NEWBORN BABY FERTILIZATION
    72. 80. IVF TÜPLERİNDEN EMBRYONİK KÖK HÜCRE ELDESİ IVF In Vitro Fertilization Thomson J & Yu SCIENCE’1998 :1998
    73. 81. ISOLATION OF EMBRYONIC STEM CELLS FROM INNER CELL MASS OF A BLASTOCYTE
    74. 82. EMBRYONIC STEM CELL COLONY
    75. 83. In-Vitro Differentiation of hESCs Embryonic Stem Cells Neurons-Tubulin + Cardiomyocytes Cardiac troponin+ Endoderm-AFP +
    76. 84. IN VIVO DIFFERENTIATION OF hESCs SCID/beige mice hESCs
    77. 85. STEM CELL TYPES <ul><li>ADULT (ASC) </li></ul><ul><li>EMBRYONIC (ESC) </li></ul><ul><li>MESENCHYMAL (MSC) </li></ul><ul><li>CORD BLOOD (CBSC) </li></ul><ul><li>INDUCIBLE PLURIPOTENT (iPS) </li></ul>
    78. 87. EMBRYONIC STEM CELL RESEARCH- VATICAN’S VIEWS SHOULD THE RESEARCHERS USE HUMAN EMBRYONIC CELLS ? ANSWER : NO IS IT ETHICAL TO CLONE EMBRYONIC CELLS AND THEN DESTROY THEM FOR RESEARCH ? ANSWER : NO IS IT ETHICAL TO USE HUMAN ESCs ? ANSWER : NO
    79. 88. Shinya Yamanaka,M.D. “ Turning Back the Cellular Clock...” Takashi K, et al,Cell 2006
    80. 89. PLURIPOTENCY FACTORS TO PRODUCE INDUCIBLE PLURIPOTENT CELLS (iPS Cells) ( Y amanaka Factors) <ul><ul><ul><ul><ul><li>OCT 3 / 4 </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>SOX 2 </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Myc </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Klf 4 </li></ul></ul></ul></ul></ul>
    81. 90. SKIN BIOPSY FROM TAIL OF MOUSE CELLS ARE SEPERATED SKIN FIBROBLASTS ARE OBTAINED NUCLEUS IS REMOVED Takashi & Yamanaka ‘2006 MOUSE OOCYTE NUCLEAR TRANSFER Enucleated Oocyte
    82. 91. “ iPS CELLS” Embryonic –like Cells GFP+ FROM SKIN to iPS CELLS Cell Cultures OCT-4 SOX-2 Kit-4 c-myc
    83. 92. November 20, 2007 Re-Programming Adult Stem Cells (Skin Cells) to Embryonic like cells Without Cloning and without Making Embryos Inducible Pluripotent Stem Cells (iPS)
    84. 93. I nducible P luripotent S tem Cells ( iPS Cells ) S.Yamanaka J.Thompson Re-Programming of Somatic Cells Rudolph Jaenisch
    85. 94. Breakthrough of the Year REPROGRAMMING CELLS Science 19 December 2008
    86. 95. STEM CELL RESEARCH
    87. 96. BENCH  BED-SIDE
    88. 97. THE STEM CELL DREAM
    89. 98. ARTIFICIAL BLADDER …April 2006 Wake Forest University Winston –Salem , California HARVARD MEDICAL SCHOOL BOSTON STEM CELLS AND REGENERATIVE MEDICINE
    90. 99. FACE TRANSPLANTATION 2005
    91. 100. CARDIAC REPAIR BY STEM CELLS
    92. 101. Growing Human MSCs on Nanofibril Scaffolds Chen FH,et al.Nature 2006
    93. 102. REGENERATIVE MEDICINE <ul><li>DISEASE </li></ul><ul><li>OSTEOARTHRITIS </li></ul><ul><li>ATHEROSCLEROSIS </li></ul><ul><li>M I </li></ul><ul><li>DIABETES </li></ul><ul><li>PARKINSON’S DIS </li></ul><ul><li>ALZHEIMER’S DIS </li></ul><ul><li>PARAPLEGIA </li></ul><ul><li>TISSUE </li></ul><ul><li>CARTILAGE *** </li></ul><ul><li>ENDOTHELIAL CELL </li></ul><ul><li>CORONARY ARTERY EC </li></ul><ul><li>PANCREAS BETA CELL </li></ul><ul><li>CNS </li></ul><ul><li>CNS </li></ul><ul><li>SPINAL CORD </li></ul>
    94. 103. STEM CELLS WHICH CELLS ? NUMBER OF CELLS ? AT WHICH STAGE OF DISEASE ? TO INDUCE A REMISSION ? OR FOR CURE ? OR FOR PALLIATION ?
    95. 104. ARE WE READY TO USE HUMAN STEM CELLS ? <ul><li>ADULT STEM CELLS : YES </li></ul><ul><li>CORD BLOOD STEM CELLS : YES </li></ul><ul><li>MESENCHYMAL STEM CELLS: YES / NO ? </li></ul><ul><li>EMBRYONIC STEM CELLS : NO </li></ul><ul><li>WHEN ? : iPS CELLS ? </li></ul><ul><li>FUTURE PROMISE </li></ul>
    96. 105. ARE WE READY TO USE EMBRYONIC STEM CELLS ? IN-VITRO YES IN-VIVO Animals Yes IN-VIVO FOR HUMANS ? NO ! NO!
    97. 106. UNANSWERED QUESTIONS : <ul><li>WHEN TO GIVE THE CELLS ? </li></ul><ul><li>WHICH CELLS TO GIVE ? </li></ul><ul><li>WHICH ROUTE TO BE USED ? </li></ul><ul><li>WHAT SHOULD BE THE OPTIMAL CELL DOSE ? </li></ul>
    98. 107. MEDICINE The Whole World Is Watching Hope—and anxiety—run high as the first clinical trial of embryonic-stem-cell therapy begins this summer. President Barack Obama’s executive order lifted restrictions on Embryonic Stem Cell Research NEWSWEEK March 30 , 2009
    99. 108. FUTURE PROSPECTS OF STEM CELL RESEARCH TO UNDERSTAND THE DEVELOPMENTAL BIOLOGY (Endoderm-Mesoderm-Ektoderm) FOR SCIENTIFIC BASIS OF CELLULAR THERAPIES TO UNDERSTAND PATHOPYSIOLOGY OF HUMAN DISEASES DRUG DISCOVERY AND TOXICOLOGY TESTING
    100. 109. More Basic Research is Needed… Too Many Hopes.... Future of Stem Cells The ideas are Great !
    101. 112. CD4+ T-CELLS CD8+ T- CELLS NK CELLS NKT CELLS Treg CELLS HEMATOPOIETIC STEM CELL HOMING AND EDUCATION AT “NICHE” HEMATOPOIETIC STEM CELL DC BONE MARROW “NICHE” MHC HSC
    102. 114. Engineering A Bioartificial Heart NATURE MEDICINE Jan 13, 2008
    103. 115. Engineering A Bioartificial Heart NATURE MEDICINE Jan 13, 2008
    104. 116. STEM CELLS : FUTURE ODESSY...... 2004 2020 – 2040 2060 … CORD BLOOD STEM CELLS EMBRYONIC STEM CELLS ADULT STEM CELLS ? ? + + +
    105. 117. RONALD REAGAN CHRISTOPHER REEVE
    106. 118. 1 JULY 2005 WHAT DO WE KNOW & WHAT DON’T WE KNOW IN SCIENCE?
    107. 121. HEMATOPOIETIC STEM CELLS “ NICHE” “ Education Sites for Stem Cells”
    108. 122. KÖK HÜCRELERİ
    109. 123. BONE MARROW STEM CELLS : How Many ?? BM Windows XP
    110. 124. REPROGRAMMING OF SOMATIC CELLS TO THE EMBRYONIC STEM CELL SOMATIC CELLS ES-like cells SOMATIC CELLS ESC FUSION ES-like Cells
    111. 125. E.DONNALL THOMAS, M.D. Emeritus Professor of Medicine University of Washington Fred Hutchinson Cancer Research Center - Seattle, USA Nobel Laureate for his contributions to Hematopoietic Stem Cell Transplantation in hematologic disorders 1990 1990
    112. 126. <ul><li>FEATURES </li></ul><ul><li>MOST BIOLOGICAL EVENTS </li></ul><ul><li>ARE SPECIFIED BY GENE </li></ul><ul><li>EXPRESSION PROGRAMS </li></ul><ul><li>LINEAGE-SPECIFICATION IS </li></ul><ul><li>CONTROLLED BY THE </li></ul><ul><li>COMBINATION OF TRANSCRIPTION </li></ul><ul><li>FACTORS (Oct 4, Sox2, Nanog) </li></ul><ul><li>REGULATION OF CHROMATIN </li></ul><ul><li>STRUCTURE PLAYS AN IMPORTANT </li></ul><ul><li>ROLE IN ESTABLISHING AND </li></ul><ul><li>MAINTAINING PROPER GENE </li></ul><ul><li>EXPRESSION </li></ul>ESC FIBROBLASTS HEPATOCYTES ADIPOCYTES NEURONS <ul><li>SELF-RENEWAL </li></ul><ul><li>PLURIPOTENCY </li></ul>EMBRYONIC STEM CELLS
    113. 127. MOUSE EMBRYONIC STEM CELLS Martin Evans’1981
    114. 128. 2007 Physiology and Medicine Oliver Smithies Univ North Carolina U.S.A. Mario Capecchi Univ of Utah U.S.A. Sir Martin Evans Cardiff Univ U.K. “ Contributions to Embryonic Stem Cell Biology and Development of Knock-Out Mouse Model to Understand Pathobiology of Diseases”
    115. 129. FUTURE OF STEM CELLS.....
    116. 130. DEVELOPMENT OF A BABY FROM EMBRYONIC STEM CELLS hESC
    117. 131. STAGES (Waves) OF HEMATOPOIESIS PRIMITIVE ERYTHROPOIESIS YOLK SAC Erytbroblasts, Macrophages Circulation / Fetal Liver TRANSIENT DEFINITIVE ERYTROPOIESIS Myelo-Erytrosid Progenitors (MEP) YOLK SAC LONG - TERM DEFINITIVE AGM YOLK SAC LARGE ARTERIES FETAL LIVER BONE MAROW Self-Renewing HSCs Lympho-Myelo-Erythroid FETAL LIVER CONCEPTION BIRTH
    118. 132. 0 20 DAY
    119. 133. BENCH  BED-SIDE
    120. 134. BREAKTHROUGHS of THE YEAR - 2007 SCIENCE December 21, 2007 318:1833 **Human Genetic Diversity and Personal “ Geneology” -Having One’s Own Genome ? *** How Adult Human Epithelial Cells could be re- programmed to act Like “Pluripotent Stem Cells” and like Embryonic Stem Cells... ** Progress in Climate Change Research and Impacts of global warming on Ecosystems and sea-ice.
    121. 135. STEM CELLS - MOUSE CLP T B NK CMP GMP G DC M MeP TR RBC HEMATOPOIETIC STEM CELLS (HSC) LONG-TERM STEM CELLS (LTSC) SHORT-TERM STEM CELLS (STSC) MULTIPOTENT PROGENITOR CELLS (MPC)
    122. 136. PROLIFERATION AND SELF-RENEWAL OF STEM CELLS IN “ NICHE” NICHE SIGNALLING TARGET CELLS WITHIN THE RANGE OF NICHE Ang-1/Tie-2 signalling and N-Cadherin contributes to NICHE - STEM CELL INTERACTION SC SC SC SIGNALLING CELLS EFFECTIVE RANGE OF SIGNALS
    123. 137. HOW WE WILL TAKE STEM CELLS TO CLINICAL MEDICINE ? <ul><li>Replacing damaged cells by “Stem Cell Transplantation” </li></ul><ul><li>As “Models” of Disease to Develop Drugs </li></ul><ul><li>Drugs Targeting Stem Cells in the Body </li></ul>
    124. 138. CLINICAL RESEARCH WITH MESENCHYMAL STEM CELLS (MSCs) <ul><li>REPAIR OF BONE DEFECTS </li></ul><ul><li>OSTEOGENESIS IMPERFECTA Rx (2002) </li></ul><ul><li>CARTILAGE REPAIR (2003) </li></ul><ul><li>TREATMENT OF GVHD AFTER ALLO STEM CELL TRANSPLANTATION (2006) </li></ul><ul><li>SKIN REPAIR AFTER BURNS (2003) </li></ul><ul><li>MUSCLE REPAIR ( 2003) </li></ul>
    125. 139. ARE WE READY TO USE STEM CELLS IN CLINICS ? <ul><li>ADULT STEM CELLS : YES </li></ul><ul><li>OTOLOGOUS HSCs : YES </li></ul><ul><li>CORD BLOOD STEM CELLS : YES </li></ul><ul><li>MESECHYMAL STEM CELLS : YES /NO </li></ul><ul><li>EMBRYONIC STEM CELLS : NO ! </li></ul><ul><li>WHEN ? : ? ? ? </li></ul>
    126. 140. UNANSWERED QUESTIONS ..2008 <ul><li>WHEN WE SHOULD GIVE STEM CELLS ? </li></ul><ul><li>WHICH CELLS WE SHOULD USE ? </li></ul><ul><li>WHAT IS THE BEST ROUTE ? </li></ul><ul><li>WHAT IS THE OPTIMAL CELL NUMBER TO GIVE ? </li></ul>
    127. 141. MEDICINE The Whole World Is Watching Hope—and anxiety—run high as the first clinical trial of embryonic-stem-cell therapy begins this summer. President Barack Obama’s executive order lifted restrictions on Embryonic Stem Cell Research NEWSWEEK March 30 , 2009
    128. 142. EMBRYONIC STEM CELLS ..Bench to Clinic ???
    129. 143. Endothelium vWF Alb/HNF1 Hepatocytes Neural cells Cardiac: No? Hemopoietic cells MESENCHYMAL STEM CELLS PDX1 TRITC Pancreas Endod *** *** *** CaPo4 Osteoblasts Chondroblasts Collagen II SM Myoblast Sm Myosin Sk Myoblast Sk Myosin
    130. 145. PROLIFERATION AND SELF-RENEWAL OF STEM CELLS IN “ NICHE” NICHE SIGNALLING TARGET CELLS WITHIN THE RANGE OF NICHE Ang-1/Tie-2 signalling and N-Cadherin contributes to NICHE - STEM CELL INTERACTION SC SC SC SIGNALLING CELLS EFFECTIVE RANGE OF SIGNALS
    131. 146. IN THE STEM CELL.... GENES mRNAs PROTEINS CELL FATE
    132. 147. MOUSE EMBRYO STEM CELL SC SC SC NEURONS Symmetric Division Asymmetric Division SC

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