Recent Advances in the Clinical Applications of Stem Cells

Simposium Asosiasi Sel PuncaSimposium Asosiasi Sel PuncaIndonesia, 2 Febr 2008Indonesia, 2 Febr 2008

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

Recent Advances in theRecent Advances in theClinical Applications ofClinical Applications of

Stem CellsStem Cells

Dr. Boenjamin Setiawan, Ph.D.Dr. Boenjamin Setiawan, Ph.D.Chairman Stem Cell and CancerChairman Stem Cell and Cancer

InstituteInstitute

dr.Boenjamin Setiawan,Ph.D.dr.Boenjamin Setiawan,Ph.D.Simposium Asosiasi Sel PuncaSimposium Asosiasi Sel PuncaIndonesia, 2 Febr 2008Indonesia, 2 Febr 2008

NationalNationalInsituteInsitute of of

HealthHealthGuidelinesGuidelines

for Stem Cellfor Stem CellResearchResearch

@ 2006 @ 2006 TereseTereseWinslowWinslow


Countries colored in brown represent about 3.5 billion people, moreCountries colored in brown represent about 3.5 billion people, morethan half the world's population. All have a permissive or flexiblethan half the world's population. All have a permissive or flexible

policy on human embryonic stem cell research and all have bannedpolicy on human embryonic stem cell research and all have bannedhuman reproductive cloning.human reproductive cloning.


World Stem Cell Research CentersWorld Stem Cell Research Centers


MengapaMengapa ABG ABG pentingpenting????

1.1. AkademiAkademi adalahadalah sumbersumber SDM SDM terdidikterdidik dandansumbersumber IPTEK IPTEK

2.2. SelamaSelama danadana pemerintahpemerintah utkutk R&D R&D kecilkecil makamakasebaiknyasebaiknya FokusFokus pd IPTEK pd IPTEK TeraplikasiTeraplikasi

3.3. BisnisBisnis adalahadalah tempattempat untukuntuk mengkonversimengkonversiIPTEK IPTEK menjadimenjadi produkproduk praktispraktis yang yang bermanfaatbermanfaatuntukuntuk masyarakatmasyarakat

4.4. Government Government adalahadalah KATALISATOR KATALISATOR untukuntukmenciptakanmenciptakan peraturanperaturan yang yang kondusifkondusif untukuntukINOVASI INOVASI melaluimelalui R&D R&D

5.5. ABG ABG harusharus membentukmembentuk kerjasamakerjasama yang yangterintegrasiterintegrasi secarasecara ““SEAMLESSSEAMLESS””

6.6. BudayaBudaya salingsaling mempersulitmempersulit harusharus diubahdiubahmenjadimenjadi BUDAYA SALING BUDAYA SALINGMEMBANTU=GOTONG ROYONGMEMBANTU=GOTONG ROYONG


The Human BodyThe Human Body

Consist of 12 Organ SystemsConsist of 12 Organ Systems Consist of 220 types of TissuesConsist of 220 types of Tissues Consist of 50-100 trillion cellsConsist of 50-100 trillion cells Consist of 100 billion neuronsConsist of 100 billion neurons Consist of 46 chromosomes (22 pairs andConsist of 46 chromosomes (22 pairs and

x and y chromosomes)x and y chromosomes) Consist of 30.000 genesConsist of 30.000 genes Consist of 3,2 billion base pairsConsist of 3,2 billion base pairs


50-100 Trillion Cells form the50-100 Trillion Cells form theBuilding Block of the Human BodyBuilding Block of the Human Body


DNA, the genetic code is principallyDNA, the genetic code is principallyfound in the Nucleus of each cellfound in the Nucleus of each cell


Consequently DNA is double stranded thatConsequently DNA is double stranded thatwound round each other in a double helixwound round each other in a double helix


Definition of stem cells: stem cells are unspecialized cells that have twodefining properties: the ability to differentiate into other cells and the ability toself-regenerate/self-renew


Stem Cells Vol. 24 No. 12 December 2006, pp. 2669 -2676Stem Cells Vol. 24 No. 12 December 2006, pp. 2669 -2676


Stem CellsStem Cellsare takenare takenfrom thefrom theInner CellInner CellMass atMass at

thetheblastocystblastocyststage andstage andcultured incultured ina Petri diska Petri disk


Adult Stem Cells: Bone MarrowAdult Stem Cells: Bone Marrow


Plasticity of Adult Stem CellsPlasticity of Adult Stem Cells


Therapeutic cloningTherapeutic cloning


Stem Cell BankingStem Cell BankingCord Blood bankingCord Blood banking is now becoming popular is now becoming popular

for for autologousautologous as well as for as well as for allogeneicallogeneic donor donorAdult Peripheral BloodAdult Peripheral Blood collection and collection and

cryopreservationcryopreservation can also be used for future can also be used for futurediseasesdiseases

Stem cells can be collectedStem cells can be collected from UCB, from UCB,AdipocytesAdipocytes and Peripheral Blood by and Peripheral Blood by ApheresisApheresis

Stem cells can be Stem cells can be CryopreservedCryopreserved for use in for use inCancers, CAD, Stroke, Diabetes, Burns, SpinalCancers, CAD, Stroke, Diabetes, Burns, SpinalCord injury, Osteoarthritis, RegenerativeCord injury, Osteoarthritis, Regenerativemedicine, etc.medicine, etc.


Target Diseases for Stem Cell TherapyBlood DiseasesBlood Diseases Bone marrow transplants (BMT) are a well known clinicalBone marrow transplants (BMT) are a well known clinical

application of application of hematopoietichematopoietic stem cell (HSC) therapy stem cell (HSC) therapy HSCsHSCs can regenerate all of the different cell types in blood can regenerate all of the different cell types in blood BMT is used for the treatment of blood cancers like leukemiaBMT is used for the treatment of blood cancers like leukemia

and lymphoma, as well as breast cancer and any otherand lymphoma, as well as breast cancer and any otherdisease requiring immune system regenerationdisease requiring immune system regeneration


The cardiovascularThe cardiovascularcirculatory systemcirculatory system’’s mains mainrole is to transportrole is to transportnutrients and oxygen tonutrients and oxygen tothe 50-100 trillion cellsthe 50-100 trillion cellsthat makes up our bodythat makes up our bodyand remove the wasteand remove the wastematerial from the body.material from the body.

The most prevalent diseaseThe most prevalent diseasethat affects the CVS is:that affects the CVS is:

1.1. AtherosclerosisAtherosclerosis2.2. HypertensionHypertension3.3. Acute myocardial infarctionAcute myocardial infarction4.4. StrokeStroke


Target Diseases for Stem Cell TherapyTarget Diseases for Stem Cell TherapyHeart DiseaseHeart Disease ES cells can be induced to form cardiac muscle cells thatES cells can be induced to form cardiac muscle cells that

actually beat in cultureactually beat in culture When transplanted into damaged hearts, these cells canWhen transplanted into damaged hearts, these cells can

form gap junctions and contract in unison withform gap junctions and contract in unison withsurrounding cellssurrounding cells

HSCsHSCs can also be grafted into damaged heart muscle and, can also be grafted into damaged heart muscle and,in this new environment, are reprogrammed to producein this new environment, are reprogrammed to produceheart cells instead of blood cellsheart cells instead of blood cells


Brief ReviewBrief Review

Endothelial Progenitor Cells

Mobilization, Differentiation, and HomingMihail Hristov; Wolfgang Erl; Peter C. WeberFrom the Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten,Ludwig-Maximilians-Universität, München, Germany

Arteriosclerosis, Thrombosis, and Vascular Biology.2003;23:1185.)© 2003 American Heart Association, Inc


Figure 1. EPCs are bone marrow-derived cells that contribute topostnatal angiogenesis. EPCs(seen in purple at A) can bemobilized from the bone marrowstroma by various growthfactors and exit throughsinusoidal vessels. Once in thebloodstream (B), EPCs begin todifferentiate (indicated by thecolor change). Subsequently,these cells home to sites ofangiogenesis in capillary beds(C) and attach to theendothelium. Unknownmechanisms drive endothelialprecursors (red) to incorporateinto the endothelial wall or pro-angiogenic monocytes (blue) tolocate behind the endothelialwall and support the stabilityand viability of the localendothelium by paracrinemechanisms

Pediatric Research 59:26R-32R (2006)© 2006 International Pediatric Research Foundation, Inc.DOI: 10.1203/01.pdr.0000203553.46471.18


Figure 3. Mechanism of EPC homing and differentiation. Recruitment andincorporation of EPCs into ischemic tissue requires a coordinated multistepprocess including mobilization, chemoattraction, adhesion, transmigration,migration, tissue invasion, and in situ differentiation. Factors that are proposed toregulate the distinct steps are indicated


ToToPreventPreventAtheroAthero--sclerosissclerosis

ControlControlcholesterocholesterol levell level

ControlControlHypertensHypertensionion

ExerciseExercise DietDiet NoNo

smokingsmoking


Differentiation of embryonicDifferentiation of embryoniccells into the cardiac lineagecells into the cardiac lineage


Physiol. Rev. 85: 1373-1416, 2005; doi:10.1152/physr “Cardiac Stem Cells andMechanisms of Myocardial Regeneration”


Therapeutic Potential of EPC in AMITherapeutic Potential of EPC in AMI

Figure 2. TherapeuticFigure 2. Therapeuticpotential of potential of EPCsEPCs..IntracoronaryIntracoronary infusion of infusion ofEPCsEPCs in patients with in patients withAMI may have theAMI may have thepotential to restorepotential to restoremyocardial function tomyocardial function tothe damaged areathe damaged area..

EPC transplantationEPC transplantationincreases left ventricularincreases left ventricularejection fraction (LVEF),ejection fraction (LVEF),coronary blood flowcoronary blood flowreserve, and myocardialreserve, and myocardialviability and decreasesviability and decreasesleft ventricular end-left ventricular end-systolic volumesystolic volume(LVESV).(LVESV).6666


Major Role CNS:Major Role CNS:The main role of the nervousThe main role of the nervoussystem is to relay electricalsystem is to relay electricalsignals through the body.signals through the body. The Thenervous system directsnervous system directsbehaviourbehaviour and movement and, and movement and,along with the endocrinealong with the endocrinesystem, controls physiologicalsystem, controls physiologicalprocesses such as digestion,processes such as digestion,circulation, etc.circulation, etc.

The most prevalent diseasesThe most prevalent diseasesthat affect the that affect the CNS is Stroke,CNS is Stroke,ParkinsonParkinson’’ss disease, disease,AlzheimerAlzheimer’’s disease, ALSs disease, ALSand Autismand Autism


Proposed Mechanism for StemProposed Mechanism for StemCells in NeurodegenerativeCells in Neurodegenerative

DiseasesDiseases Implanted stem cells migrated &Implanted stem cells migrated &

integrated extensively throughout theintegrated extensively throughout thebrainbrain

Some of the transplanted cells replacedSome of the transplanted cells replaceddamaged nerve cells and transmitteddamaged nerve cells and transmittednerve impulsesnerve impulses integrate integrate electricallyelectricallyand and functionallyfunctionally into a diseased braininto a diseased brain

stem cells employ stem cells employ multiple mechanismsmultiple mechanisms not just cell replacementnot just cell replacement - which - whichcollaborate to benefit diseasecollaborate to benefit diseaseLee et al, Nature 2007


Brain Cell TransplantationBrain Cell Transplantation

The identification and The identification and localisationlocalisation of neural stem cells, of neural stem cells,both embryonic and adult, has been a major focus ofboth embryonic and adult, has been a major focus ofcurrent research.current research.

Potential targets of neural stem cell transplantsPotential targets of neural stem cell transplants

1. include stroke, 2. spinal cord injury,1. include stroke, 2. spinal cord injury,andand

3. neurodegenerative diseases such as3. neurodegenerative diseases such asParkinson's Disease, 4. AlzheimerParkinson's Disease, 4. Alzheimer

Stem cells can provide dopamine - a chemical lacking inStem cells can provide dopamine - a chemical lacking invictims of Parkinson's Diseasevictims of Parkinson's Disease

Over 250 patients have already been transplanted withOver 250 patients have already been transplanted withhuman fetal tissuehuman fetal tissue


Target Diseases for Stem Cell TherapyTarget Diseases for Stem Cell Therapy

Brain and Spinal CordBrain and Spinal CordInjuryInjury

Neural stem cells can beNeural stem cells can beisolated from adult brains orisolated from adult brains orgenerated from ES cells ingenerated from ES cells incultureculture

HSCsHSCs can also be can also betransplanted into the braintransplanted into the brainwhere they arewhere they arereprogrammed to generatereprogrammed to generateneurons and neurons and glialglial cells cells

Potential applicationsPotential applicationsinclude Parkinsoninclude Parkinson’’s disease,s disease,ALS, HuntingtonALS, Huntington’’s disease,s disease,stroke, Alzheimerstroke, Alzheimer’’s disease,s disease,paralysisparalysis

Animal and early humanAnimal and early humantrials are underwaytrials are underway

Simposium Asosiasi Sel PuncaSimposium Asosiasi Sel PuncaIndonesia, 2 Febr 2008Indonesia, 2 Febr 2008

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

IschemicIschemicStrokeStroke


CerebralCerebralHemorrhHemorrhageage


Spinal Cord InjuriesSpinal Cord InjuriesHwang Mi-Soon: SouthKorea

Paralyzed 19 years

Multipotent adult stem cellsinjectedinto her spinal cord

Currently: debilitating pain

Published in 2005 (Cytotherapy)


ParkinsonParkinson’’s Disease :s Disease :Degeneration of brain cellsDegeneration of brain cells

Cells in theCells in thesubstantiasubstantia nigranigra

Loss of theLoss of thechemicalchemicaldopaminedopamine

No clearNo clearreason whyreason why


Osteoarthritis and AutoimmuneOsteoarthritis and AutoimmuneDiseasesDiseases

MesenchymalMesenchymalstem cells arestem cells areused to beused to beinserted into theinserted into thesynovialsynovial cavity cavitywhere theywhere theytransdifferentiatetransdifferentiateintointochondroblastschondroblastsand form newand form newcartilagecartilage


Osteoarthritis of the Knee JointOsteoarthritis of the Knee Joint

MesenchymalMesenchymal stem stemcells are implantedcells are implantedinto ainto abiodegradablebiodegradablescaffold andscaffold andinserted into theinserted into thesynovialsynovial cavity cavitywhere they willwhere they willtransdifferentiatetransdifferentiateinto new cartilageinto new cartilage


Target Diseases for Stem Cell TherapyTarget Diseases for Stem Cell Therapy

Type 1 DiabetesType 1 Diabetes

Patients lack pancreaticPatients lack pancreaticbeta cells and cannotbeta cells and cannotproduce insulinproduce insulin

Insulin-producingInsulin-producingstructures similar tostructures similar topancreatic islets have beenpancreatic islets have beengenerated from mouse ESgenerated from mouse EScells in culturecells in culture

It may also be possible toIt may also be possible toisolate pancreatic stemisolate pancreatic stemcells from adult tissuecells from adult tissue

Early stage of developmentEarly stage of development


Stem Cell BankingStem Cell BankingCord Blood bankingCord Blood banking is now becoming popular for is now becoming popular for

autologousautologous as well as for as well as for allogeneicallogeneic donor donorAdult Peripheral BloodAdult Peripheral Blood collection and collection and

cryopreservationcryopreservation can also be used for future can also be used for futurediseasesdiseases

Endothelial progenitor cells and Endothelial progenitor cells and MesenchymalMesenchymalstem cellsstem cells are potentially are potentially usefullusefull for many clinical for many clinicalapplicationsapplications

Stem cells can be collectedStem cells can be collected from UCB, from UCB,AdipocytesAdipocytes and Peripheral Blood by and Peripheral Blood by ApheresisApheresis

Stem cells can be Stem cells can be CryopreservedCryopreserved for use in for use inCancers, CAD, Stroke, Diabetes, Burns, Spinal CordCancers, CAD, Stroke, Diabetes, Burns, Spinal Cordinjury, Osteoarthritis, Regenerative medicine, etc.injury, Osteoarthritis, Regenerative medicine, etc.


ConclusionsConclusionsAdult stem cellsAdult stem cells can be obtained from can be obtained from

BM, Fetus, BM, Fetus, hUCBhUCB, , AdipocytesAdipocytes and andPeripheral blood, It will not create anyPeripheral blood, It will not create anyethical problemsethical problems

Adult stem cellsAdult stem cells from fetuses and from fetuses and hUCBhUCBare the most are the most PLASTICPLASTIC

Embryonic stem cellsEmbryonic stem cells obtained from the obtained from theINNER CELL MASS for THERAPEUTICINNER CELL MASS for THERAPEUTICpurposes are allowed in 38 countries (UK,purposes are allowed in 38 countries (UK,Sweden, Belgium, Netherland, China, India,Sweden, Belgium, Netherland, China, India,Korea, Taiwan, Singapore, Malaysia etc.)Korea, Taiwan, Singapore, Malaysia etc.)

Embryonic stem cellsEmbryonic stem cells for reproductive cloning for reproductive cloningis not allowed in ALL COUNTRIESis not allowed in ALL COUNTRIES


5. 5. MesenchymalMesenchymal Stem Cells from BM, Stem Cells from BM,Fetuses, Fetuses, hUCBhUCB, can be used as, can be used asProgenitor Neuronal CellsProgenitor Neuronal Cells for fortransplantation in Neurodegenerativetransplantation in NeurodegenerativeDiseases.Diseases.

6. 6. EPCsEPCs as well as MSC from BM, as well as MSC from BM, hUCBhUCB,,AdipocytesAdipocytes and peripheral blood and peripheral blood can be can beused for AMIused for AMI

7. 7. Stem Cell ResearchStem Cell Research should become a should become aPRIORITY to be carried out in IndonesiaPRIORITY to be carried out in Indonesia

8. 8. Academic Institutions, Business andAcademic Institutions, Business andGovernment (ABG)Government (ABG) must Cooperate Closely must Cooperate Closelyto Stimulate RND for the Benefit of Societyto Stimulate RND for the Benefit of Society

Recent Advances in the Clinical Applications of Stem Cells

Health & Medicine

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