National Insitute of Health Guidelines for Stem Cell Research
Recent Advances in the Clinical Applications of Stem Cells Dr. Boenjamin Setiawan, Ph.D. Chairman Stem Cell and Cancer Institute Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Countries colored in brown represent about 3.5 billion people, more more than half the world's population. All have a permissive or flexible flexible policy on human embryonic stem cell research and all have banned
@ 2006 Terese Winslow
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
World Stem Cell Research Centers
human reproductive cloning.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
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Mengapa ABG penting?? Akademi adalah sumber SDM terdidik dan sumber IPTEK Selama dana pemerintah utk R&D kecil maka 2. sebaiknya Fokus pd IPTEK Teraplikasi Bisnis adalah tempat untuk mengkonversi 3. IPTEK menjadi produk praktis yang bermanfaat untuk masyarakat Government adalah KATALISATOR untuk 4. menciptakan peraturan yang kondusif untuk INOVASI melalui R&D ABG harus membentuk kerjasama yang 5. terintegrasi secara “SEAMLESS” SEAMLESS” Budaya saling mempersulit harus diubah 6. menjadi BUDAYA SALING MEMBANTU=GOTONG Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. ROYONG Indonesia, 2 Febr 2008 1.
5050-100 Trillion Cells form the Building Block of the Human Body
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
The Human Body z Consist
of 12 Organ Systems z Consist of 220 types of Tissues z Consist of 5050-100 trillion cells z Consist of 100 billion neurons z Consist of 46 chromosomes (22 pairs and x and y chromosomes) z Consist of 30.000 genes z Consist of 3,2 billion base pairs Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
DNA, the genetic code is principally found in the Nucleus of each cell
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
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Consequently DNA is double stranded that wound round each other in a double helix
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
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 dr.Boenjamin Setiawan,Ph.D. self-regenerate/self-renew
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Stem Cells Vol. 24 No. 12 December 2006, pp. 2669 -2676
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
dr.Boenjamin Setiawan,Ph.D.
Stem Cells are taken from the Inner Cell Mass at the blastocyst stage and cultured in a Petri disk
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
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Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Adult Stem Cells: Bone Marrow
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Plasticity of Adult Stem Cells
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
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Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
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Therapeutic cloning
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Stem Cell Banking 1. 2.
3. 4.
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 Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
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The cardiovascular
z
Target Diseases for Stem Cell Therapy
Blood Diseases Bone marrow transplants (BMT) are a well known clinical application of hematopoietic stem cell (HSC) therapy z HSCs can regenerate all of the different cell types in blood z 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 z
z
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
1. 2. 3. 4.
circulatory system’ system’s main role is to transport nutrients and oxygen to the 5050-100 trillion cells that makes up our body and remove the waste material from the body. The most prevalent disease that affects the CVS is: Atherosclerosis Hypertension Acute myocardial infarction Stroke
dr.Boenjamin Setiawan,Ph.D.
Target Diseases for Stem Cell Therapy Heart Disease ES cells can be induced to form cardiac muscle cells that actually beat in culture z When transplanted into damaged hearts, these cells can form gap junctions and contract in unison with surrounding cells z HSCs can also be grafted into damaged heart muscle and, in this new environment, are reprogrammed to produce heart cells instead of blood cells z
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
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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 Indonesia, 2 Febr 2008
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Pediatric Research 59:26R-32R (2006) © 2006 International Pediatric Research Foundation, Figure Inc. 1. EPCs are bone marrowDOI: 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 proangiogenic monocytes (blue) to locate behind the endothelial wall and support the stability and viability of the local endothelium Simposium Asosiasi Sel Punca dr.Boenjamin Setiawan,Ph.D. Indonesia, 2 Febr 2008 by paracrine mechanisms
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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 Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
z
1.
2.
3. 4. 5. Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
To Prevent AtheroAtherosclerosis Control cholestero l level Control Hypertens ion Exercise Diet No smoking
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Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Differentiation of embryonic cells into the cardiac lineage
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
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Physiol. Rev. 85: 1373-1416, 2005; doi:10.1152/physr “Cardiac Stem Cells and Mechanisms of Myocardial Regeneration”
Therapeutic Potential of EPC in AMI z
Figure 2. Therapeutic potential of EPCs. EPCs. Intracoronary infusion of EPCs in patients with AMI may have the potential to restore myocardial function to the damaged area. area.
EPC transplantation increases left ventricular ejection fraction (LVEF), coronary blood flow reserve, and myocardial viability and decreases left ventricular endendsystolic volume dr.Boenjamin Setiawan,Ph.D. (LVESV).66 (LVESV).66 z
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
z 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. z The most prevalent diseases that affect the CNS is Stroke, Parkinson’ Parkinson’s disease,
Alzheimer’ Alzheimer’s disease, ALS and Autism
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
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Proposed Mechanism for Stem Cells in Neurodegenerative Diseases
z Implanted
stem cells migrated & integrated extensively throughout the brain z Some of the transplanted cells replaced damaged nerve cells and transmitted nerve impulsesÆ impulsesÆ integrate electrically and functionally into a diseased brain z stem cells employ multiple mechanisms Æ not just cell replacement - which collaborate to benefit diseaseLee et al, Nature 2007 Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Brain Cell Transplantation z
z
z z z z
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 Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Ischemic Stroke
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 z HSCs can also be transplanted into the brain where they are reprogrammed to generate neurons and glial cells z Potential applications include Parkinson’ Parkinson’s disease, ALS, Huntington’ Huntington’s disease, stroke, Alzheimer’ Alzheimer’s disease, paralysis z Animal and early human Simposiumare Asosiasi underway Sel Punca dr.Boenjamin Setiawan,Ph.D. trials z
Indonesia, 2 Febr 2008
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
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z Cerebral
Hemorrh age
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 Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Published in 2005 (Cytotherapy)
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Parkinson’ Parkinson’s Disease : Degeneration of brain cells z
Cells in the
z
Loss of the chemical
substantia nigra
dopamine
z
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
No clear reason why
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Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
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Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Osteoarthritis and Autoimmune Diseases z Mesenchymal
stem cells are used to be inserted into the synovial cavity where they transdifferentiate into chondroblasts and form new cartilage
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
16
Osteoarthritis of the Knee Joint z 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 Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Target Diseases for Stem Cell Therapy
Type 1 Diabetes Patients lack pancreatic beta cells and cannot produce insulin z InsulinInsulin-producing structures similar to pancreatic islets have been generated from mouse ES cells in culture z It may also be possible to isolate pancreatic stem cells from adult tissue z Early stage of development z
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
17
Conclusions
Stem Cell Banking 1. 2.
3.
4. 5.
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.
5. Mesenchymal Stem Cells from BM, Fetuses, hUCB, hUCB, can be used as Progenitor Neuronal Cells for transplantation in Neurodegenerative Diseases. 6. EPCs as well as MSC from BM, hUCB, 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 Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
1.
2. 3.
4.
Adult stem cells can be obtained from BM, Fetus, hUCB, 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 Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
Simposium Asosiasi Sel Punca Indonesia, 2 Febr 2008
dr.Boenjamin Setiawan,Ph.D.
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