Recent Advances in the Clinical Applications of Stem Cells

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Recent Advances in the Clinical Applications of Stem Cells

  1. 1. Recent Advances in the Clinical Applications of Stem Cells Dr. Boenjamin Setiawan, Ph.D. Chairman Stem Cell and Cancer Institute Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  2. 2. National Insitute of Health Guidelines for Stem Cell Research @ 2006 Terese Winslow Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  3. 3. Countries colored in brown represent about 3.5 billion people, more than half the world's population. All have a permissive or flexible policy on human embryonic stem cell research and all have banned human reproductive cloning. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  4. 4. World Stem Cell Research Centers Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  5. 5. Mengapa ABG penting?? 1. Akademi adalah sumber SDM terdidik dan sumber IPTEK 2. Selama dana pemerintah utk R&D kecil maka sebaiknya Fokus pd IPTEK Teraplikasi 3. Bisnis adalah tempat untuk mengkonversi IPTEK menjadi produk praktis yang bermanfaat untuk masyarakat 4. Government adalah KATALISATOR untuk menciptakan peraturan yang kondusif untuk INOVASI melalui R&D 5. ABG harus membentuk kerjasama yang terintegrasi secara “SEAMLESS” 6. Budaya saling mempersulit harus diubah menjadi BUDAYA SALING Indonesia, MEMBANTU=GOTONG ROYONG Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. 2 Febr 2008
  6. 6. The Human Body  Consist of 12 Organ Systems  Consist of 220 types of Tissues  Consist of 50-100 trillion cells  Consist of 100 billion neurons  Consist of 46 chromosomes (22 pairs and x and y chromosomes)  Consist of 30.000 genes  Consist of 3,2 billion base pairs Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  7. 7. 50-100 Trillion Cells form the Building Block of the Human Body Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  8. 8. DNA, the genetic code is principally found in the Nucleus of each cell Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  9. 9. Consequently DNA is double stranded that wound round each other in a double helix Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  10. 10. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  11. 11. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  12. 12. Definition of stem cells: stem cells are unspecialized cells that have two defining properties: the ability to differentiate into other cells and the ability to Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008 self-regenerate/self-renew
  13. 13. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  14. 14. Stem Cells Vol. 24 No. 12 December 2006, pp. 2669 -2676 Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  15. 15. Stem Cells are taken from the Inner Cell Mass at the blastocyst stage and cultured in Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008 dr.Boenjamin Setiawan,Ph.D. a Petri disk
  16. 16. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
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  18. 18. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  19. 19. Adult Stem Cells: Bone Marrow Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  20. 20. Plasticity of Adult Stem Cells Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  21. 21. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  22. 22. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  23. 23. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  24. 24. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  25. 25. Therapeutic cloning Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  26. 26. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  27. 27. Stem Cell Banking  Cord  Blood banking is now becoming popular for autologous as well as for allogeneic donor  Adult Peripheral Blood collection and cryopreservation can also be used for future diseases  Stem cells can be collected from UCB, Adipocytes and Peripheral Blood by Apheresis  Stem cells can be Cryopreserved for use in  Cancers, CAD, Stroke, Diabetes, Burns, Spinal Cord injury, Osteoarthritis, Regenerative medicine, etc. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  28. 28. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  29. 29. Target Diseases for Stem Cell Therapy Blood Diseases  Bone marrow transplants (BMT) are a well known clinical application of hematopoietic stem cell (HSC) therapy  HSCs can regenerate all of the different cell types in blood  BMT is used for the treatment of blood cancers like leukemia and lymphoma, as well as breast cancer and any other disease requiring immune system regeneration Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  30. 30.  The cardiovascular circulatory system’s main role is to transport nutrients and oxygen to the 50-100 trillion cells that makes up our body and remove the waste material from the body.  The most prevalent disease that affects the CVS is: 1. Atherosclerosis 2. Hypertension 3. Acute myocardial infarction Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008 4. Stroke dr.Boenjamin Setiawan,Ph.D.
  31. 31. Target Diseases for Stem Cell Therapy Heart Disease  ES cells can be induced to form cardiac muscle cells that actually beat in culture  When transplanted into damaged hearts, these cells can form gap junctions and contract in unison with surrounding cells  HSCs can also be grafted into damaged heart muscle and, in this new environment, are reprogrammed to produce heart cells instead of blood cells Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  32. 32. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  33. 33. Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1185.) © 2003 American Heart Association, Inc Brief Review Endothelial Progenitor Cells Mobilization, Differentiation, and Homing Mihail Hristov; Wolfgang Erl; Peter C. Weber From the Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Ludwig-Maximilians-Universität, München, Germany Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  34. 34. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  35. 35. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  36. 36. Pediatric Research 59:26R-32R (2006) © 2006 International Pediatric Research Foundation,Figure 1. EPCs are bone marrow- Inc. DOI: 10.1203/01.pdr.0000203553.46471.18 derived cells that contribute to postnatal angiogenesis. EPCs (seen in purple at A) can be mobilized from the bone marrow stroma by various growth factors and exit through sinusoidal vessels. Once in the bloodstream (B), EPCs begin to differentiate (indicated by the color change). Subsequently, these cells home to sites of angiogenesis in capillary beds (C) and attach to the endothelium. Unknown mechanisms drive endothelial precursors (red) to incorporate into the endothelial wall or pro- angiogenic monocytes (blue) to locate behind the endothelial wall and support the stability and viability of the local Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. endothelium by paracrine Indonesia, 2 Febr 2008 mechanisms
  37. 37. Figure 3. Mechanism of EPC homing and differentiation. Recruitment and incorporation of EPCs into ischemic tissue requires a coordinated multistep process including mobilization, chemoattraction, adhesion, transmigration, migration, tissue invasion, and in situ differentiation. Factors that are proposed to regulate the distinct steps are indicated Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
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  40. 40.  To Prevent Athero- sclerosis  Control  cholestero l level  Control Hypertens ion  Exercise  Diet   No Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008 dr.Boenjamin Setiawan,Ph.D. smoking
  41. 41. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  42. 42. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  43. 43. Differentiation of embryonic cells into the cardiac lineage Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  44. 44. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  45. 45. Physiol. Rev. 85: 1373-1416, 2005; doi:10.1152/physr “Cardiac Stem Cells and Mechanisms of Myocardial Regeneration” Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  46. 46. Therapeutic Potential of EPC in AMI  Figure 2. Therapeutic potential of EPCs. Intracoronary infusion of EPCs in patients with AMI may have the potential to restore myocardial function to the damaged area.  EPC transplantation increases left ventricular ejection fraction (LVEF), coronary blood flow reserve, and myocardial viability and decreases left ventricular end- Simposium Asosiasi Sel Punca systolic volume dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008 (LVESV).66
  47. 47. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  48. 48.  Major Role CNS: The main role of the nervous system is to relay electrical signals through the body. The nervous system directs behaviour and movement and, along with the endocrine system, controls physiological processes such as digestion, circulation, etc.  The most prevalent diseases that affect the CNS is Stroke, Parkinson’s disease, Alzheimer’s disease, ALS and Autism Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  49. 49. Proposed Mechanism for Stem Cells in Neurodegenerative Diseases  Implanted stem cells migrated & integrated extensively throughout the brain  Some of the transplanted cells replaced damaged nerve cells and transmitted nerve impulses integrate electrically and functionally into a diseased brain  stem cells employ multiple mechanisms  not just cell replacement - which collaborate to benefit disease et al, Nature 2007 Simposium Asosiasi Sel Punca Lee dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  50. 50. Brain Cell Transplantation  The identification and localisation of neural stem cells, both embryonic and adult, has been a major focus of current research.  Potential targets of neural stem cell transplants  1. include stroke, 2. spinal cord injury, and  3. neurodegenerative diseases such as Parkinson's Disease, 4. Alzheimer  Stem cells can provide dopamine - a chemical lacking in victims of Parkinson's Disease  Over 250 patients have already been transplanted with human fetal tissue Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  51. 51. Target Diseases for Stem Cell Therapy Brain and Spinal Cord Injury  Neural stem cells can be isolated from adult brains or generated from ES cells in culture  HSCs can also be transplanted into the brain where they are reprogrammed to generate neurons and glial cells  Potential applications include Parkinson’s disease, ALS, Huntington’s disease, stroke, Alzheimer’s disease, paralysis  AnimalFebr 2008 Punca Simposium Asosiasi Sel early human Indonesia, 2 and dr.Boenjamin Setiawan,Ph.D. trials are underway
  52. 52. Ischemic Stroke Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  53. 53.  Cerebral Hemorrh age Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  54. 54. Spinal Cord Injuries Hwang Mi-Soon: South Korea Paralyzed 19 years Multipotent adult stem cells injected into her spinal cord Currently: debilitating pain Simposium Asosiasi Sel Punca Published in 2005 (Cytotherapy) dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  55. 55. Parkinson’s Disease : Degeneration of brain cells  Cells in the substantia nigra  Loss of the chemical dopamine  No clear reason why Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  56. 56. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
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  59. 59. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
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  63. 63. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  64. 64. Osteoarthritis and Autoimmune Diseases  Mesenchymal stem cells are used to be inserted into the synovial cavity where they transdifferentiate into chondroblasts and form new Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008 dr.Boenjamin Setiawan,Ph.D. cartilage
  65. 65. Osteoarthritis of the Knee Joint  Mesenchymal stem cells are implanted into a biodegradable scaffold and inserted into the synovial cavity where they will transdifferentiate into new cartilage Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  66. 66. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  67. 67. Target Diseases for Stem Cell Therapy Type 1 Diabetes  Patients lack pancreatic beta cells and cannot produce insulin  Insulin-producing structures similar to pancreatic islets have been generated from mouse ES cells in culture  It may also be possible to isolate pancreatic stem cells from adult tissue  Early stage of development Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  68. 68. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  69. 69. Stem Cell Banking  Cord  Blood banking is now becoming popular for autologous as well as for allogeneic donor  Adult Peripheral Blood collection and cryopreservation can also be used for future diseases  Endothelial progenitor cells and Mesenchymal stem cells are potentially usefull for many clinical applications  Stem cells can be collected from UCB,  Adipocytes and Peripheral Blood by Apheresis  Stem cells can be Cryopreserved for use in Cancers, CAD, Stroke, Diabetes, Burns, Spinal Cord injury, Osteoarthritis, Regenerative medicine, etc. Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008 dr.Boenjamin Setiawan,Ph.D.
  70. 70. Conclusions  Adult  stem cells can be obtained from BM, Fetus, hUCB, Adipocytes and Peripheral blood, It will not create any ethical problems  Adult stem cells from fetuses and hUCB are the most PLASTIC  Embryonic stem cells obtained from the INNER CELL MASS for THERAPEUTIC purposes are allowed in 38 countries (UK, Sweden, Belgium, Netherland, China, India, Korea, Taiwan, Singapore, Malaysia etc.)  Embryonic stem cells for reproductive cloning  is not allowed in ALL COUNTRIES Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  71. 71. 5. Mesenchymal Stem Cells from BM, Fetuses, hUCB, can be used as Progenitor Neuronal Cells for transplantation in Neurodegenerative Diseases. 6. EPCs as well as MSC from BM, hUCB, Adipocytes and peripheral blood can be used for AMI 7. Stem Cell Research should become a PRIORITY to be carried out in Indonesia 8. Academic Institutions, Business and Government (ABG) must Cooperate Closely to Stimulate RND for the Benefit of Society Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008
  72. 72. Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008

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