Date of Birth : Tegal (Central Java), 23 September 1933 QUALIFICATIONS:

1. Curriculum Vitae Dr. Boenjamin Setiawan, Ph.D. Date of Birth : Tegal (Central Java), 23 September 1933 QUALIFICATIONS: 1938– 1947: Elementary School 1948– 1951: High School 1951 – 1958: Medical Faculty at University of Indonesia, Graduated in 1958 1958 – 1961:University of California, San Francisco, Ph.D. degree in Pharmacology. Thesis: The Inhibition of Alcohol Dehydrogenase by Chlorpromazine and other PhenothazineDerivates MEMBERSHIP: 1970 - 1990 : Member/Founder YayasanPengembanganSumberDayaManusia 1996 - 2006: Member KomnasPerempuan 1985 - Present: Member/Founder YayasanPengembanganKreativitas 1990 - Present: Member YayasanKeanekaragamanHayati Indonesia 1990 - Present : Ketua Yayasan Pendidikan Kalbe 2005 - Present : Member Komnas Lansia 2005 - Present: Ernst & Young Lifetime Entrepreneurial Award 2008 - Present: Vice Chairman of Advisory Board, Indonesian Stem Cell Association / Asosiasi Sel Punca Indonesia (ASPI) 2010 : Honorary Reviewer Ristek Kalbe Science Award (RKSA)

2. Slowing Down The Aging Process with Stem CellsBoenjaminSetiawan, dr., Ph.D.Chairman of Scientific Advisory BoardStem Cell and Cancer Institute Boenjamin Setiawan,dr.,Ph.D.

3. When Does AgeingBegin? • Ageingbegins the day we are born • There is no single measure of how “old” a person is • Ageingis highly individualized • Ageingproceeds at different rates in different people, and within different systems of the body • Ageing is GENETIC and the secret is stored in the DNA

4. Why Do People Age? Many theories to include: • Hereditary Factors, stored in DNA • Loss of cellular mass and ability of cells to divide and replicate, STEM CELLS • Accumulation of waste materials that clog cells and cause them to die, TELOMERASE • Oxidative damage as a result of normal METABOLISM caused by FREE RADICALS, ROS, use ANTIOXIDANTS • Changes in structure of connective tissue No single theory adequately describes the aging process

5. Normal Changes of Aging • Physical changes related to “Normal” aging ARE NOT disease • Changes occur in most body systems to include: 1. Sensory System: Hearing, Vision, Balance, Taste buds, etc. 2. Cardiovascular system 3. Central Nervous System 4. Skin, Muscles and Bones 5.Digestion system 6. Respiratory system 7. Immune system 8. Endocrine system 9. All Organ System starts to Degenerate

6. The Theories and Major Causes of Age-related Death are: 1. Oxidative Damage – ANTI-OXIDANTS 2. Cell DNA Damage 3. Mitochondrial Damage 4. Lipofuscin Accumulation 5. Chronic Inflammation - MESENCHYMAL STEM CELLS 6. Immune System Compromise - MSC 7. Neurological Degeneration 8. Declines in Hormone Levels–Growth Hormone, Testosteron 9. Susceptibility to Cancers 10. Susceptibility to Cardiovascular Disease 11. Telomere Shortening and Damage 12. Programmed Epigenomic Changes 13. Stem Cell Supply Chain Breakdown–STEM CELL SUPPLY Boenjamin Setiawan,dr.,Ph.D.

7. The Life Sciences Revolution in the News • Stem Cell Therapy • Regenerative Medicine • Human Cloning • Genomics • Induced Pluripotent SC • The Human Genome Project • Genetically Modified Crops • Biological Agents in Bioterrorism Special edition to celebrate the 50th anniversary of the discovery of DNA: February 17, 2003 Boenjamin Setiawan,dr.,Ph.D.

8. Global Aging Boenjamin Setiawan,dr.,Ph.D.

9. “Force of mortality” (hazard rate) increases with age Boenjamin Setiawan,dr.,Ph.D.

10. Aging is a Very General Phenomenon! Boenjamin Setiawan,dr.,Ph.D.

11. According to Reliability Theory:Aging is NOT just growing oldInsteadAging is a degradation to failure: becoming sick, frail and dead • 'Healthy aging' is an oxymoron like a healthy dying or a healthy disease • More accurate terms instead of 'healthy aging' would be a delayed aging, postponed aging, slow aging, or negligible aging (senescence) Boenjamin Setiawan,dr.,Ph.D.

12. World’s oldest person celebrates 129th birthday, died March 2007 According to national records, Hernandez was born on May 3, 1878, in one of the country's central provinces, where she gave birth to 13 children. She now has 60 grandchildren, 80 great-grandchildren and 25 great-great grandchildren. Boenjamin Setiawan,dr.,Ph.D.

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14. 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 Boenjamin Setiawan,dr.,Ph.D.

15. 50-100 Trillion Cells form the Building Block of the Human Body Boenjamin Setiawan,dr.,Ph.D.

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17. How are ES Cells Generated? Multiple embryos are produced in vitro for clinical purposes.Donated surplus embryos are used as a source of ES cells.These surplus embryos would otherwise be discarded or remain unused Boenjamin Setiawan,dr.,Ph.D.

18. Fertilized Embryos Are Allowed to Divide Several Times in Culture Boenjamin Setiawan,dr.,Ph.D.

19. Harvesting ES Cells The blastocyst is the stage of development (~1,000 cells) at which the embryos inner cell mass (ICM) forms. It is the ICM that harbors ES cells. Stem cells exist only fleetingly at this stage of development Boenjamin Setiawan,dr.,Ph.D.

20. Where Are Early Stem Cells Found? • Who did it first? • In 1998, Prof. James Thomson,U. Wisconsin research team isolated stem cells from IVF-blastocysts 5 days of development Boenjamin Setiawan,dr.,Ph.D.

21. Stem Cells are taken from the Inner Cell Mass at the blastocyst stage and cultured in a Petri disk Boenjamin Setiawan,dr.,Ph.D.

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26. Sources of stem cells Embryonic Stemcells: - spare embryos, from IVF - special purpose embryos - cloned embryos Adult stem cells:- adult tissue, - Bone marrow, Peripheral blood, Adipose tissue, Lung, Liver, Pericytes Other sources: - aborted fetuses - umbilical cords Boenjamin Setiawan,dr.,Ph.D.

27. Stem Cell and Cancer Institute Capabilities, SCI (Indonesia) • Culturing and multiplications of hUCB stem cells for BURNS and CHRONIC WOUNDS • Culturing and multiplications of Chondrocytes for Osteoarthritis • Culturing and multiplication of AutologousMNC/EPCfrom Peripheral blood for AMI and Heart failure • Culturing hUC. MSC for Stroke and Cerebral Palsy 5SCIDeveloped VascGrow a Cocktail to Grow and Differentiate Human EPC Boenjamin Setiawan,dr.,Ph.D.

28. Cell Banking, Processing and Analysis Facility Reagents and consumables • Controlled storage • Controlled temperature for refrigerators • Controlled SOPs for procedures • Certificate of analysis Boenjamin Setiawan,dr.,Ph.D.

29. Stem Cells Isolation from Lipoaspirates for further Research Application • - Routinely prepares Mesenchymal Stem Cell isolation from lipoaspirate • Collaborates with several Plastic surgeons • - On going research to study several distinct molecules Boenjamin Setiawan,dr.,Ph.D.

30. Cell Banking, Processing and Analysis Facility • Clinical Grade • Standardized procedures • Provide cells for stem cells clinical trials • Allogeneic & autologous Cryopreservation facility (vapour phase) Controlled Transported samples (temperature logger) Complete report of product quality and evaluation  GMP Facility Boenjamin Setiawan,dr.,Ph.D.

31. SCI projects Stem Cell Research Division 1. Cell Analysis, Processing and Banking Facility 2. Immunogenicity Characterization of Mononucleated Cells Originated from UCB - scientific explanation for allogeneic UCB MNC therapy 3. Endothelial Progenitors Cell Expansion • Determination of EPCs frequency as biological marker for vascular function & cardiovascular disease risk • MI, Rejuvenation, & anti-aging 4. Stem Cells Isolation from Lipoaspirates for further Research Application Boenjamin Setiawan,dr.,Ph.D.

32. Applications: Heart Failure in Harapan Kita Hospital 2 EPC culture Medium 1 Blood Collection 3 VascGrow Ready for EPC implantation Cells are collected and washed Boenjamin Setiawan,dr.,Ph.D.

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34. COMMERCIALIZATION Boenjamin Setiawan,dr.,Ph.D. Windpipe Transplant

35. Beating Rat Heart Created In Laboratory: Method May Revolutionize How Organ Tissues Are Developed ScienceDaily (Jan. 14, 2008) — University of Minnesota researchers have created a beating RAT heart in the laboratory Rat heart decellularization(top three images), and during recellularization (bottom two images). Experiment and photos: November 2006. (Credit: Thomas Matthiesen) Boenjamin Setiawan,dr.,Ph.D.

36. Stages of Regenerative Medicine, 5R • Repair, Molecular Changes in the Microenvironment through Paracrine Secretions of STEM CELLS • Replacementof dead cells with somatic stem cells in affected tissues/organs • Regenerationof all the functions of the affected tissues/organs • Rehabilitation of all the tissues/organs in a multi-organ failure • Rejuvenationthe dream of everybody to be able to rejuvenate all the molecules, cells, tissues/organs of the body through changes/reprogramming of the DNA molecule with a protein cocktail (elixir of life) Boenjamin Setiawan,dr.,Ph.D.

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39. 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 Boenjamin Setiawan,dr.,Ph.D.

40. 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 4. Stroke Boenjamin Setiawan,dr.,Ph.D.

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43. Major Role of 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 Boenjamin Setiawan,dr.,Ph.D.

44. The brain microvascular endothelium constitutes a major exchange area between the blood and the brain: it forms a physiological barrier, known as the blood-brain barrier (BBB), which plays a central role in maintaining cerebral homeostasis. Boenjamin Setiawan,dr.,Ph.D.

45. Spinal Cord Injuries Hwang Mi-Soon: South Korea Paralyzed 19 years Multipotent adult stem cells injected into her spinal cord Currently: debilitating pain Published in 2005 (Cytotherapy) Boenjamin Setiawan,dr.,Ph.D.

46. Ischemic Stroke Boenjamin Setiawan,dr.,Ph.D.

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49. 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 Boenjamin Setiawan,dr.,Ph.D.

50. Osteoarthritis and Autoimmune Diseases • Mesenchymal stem cells are used to be inserted into the synovial cavity where they transdifferentiate into chondroblasts and form new cartilage Boenjamin Setiawan,dr.,Ph.D.