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Iraq - Erbil 2013
MarwanAlhalabi MDPhDProfessorinReproductiveMedicineFacultyofMedicineDamascusUniversity
And
MedicalDirectorOrientHospitalAssistedReproductionCenterDamascus– Syria
Andalus University2015
1 – THE RIGHT GROWTH FACTORS
2 – THE RIGHT RECEPTORS
3 – THE RIGHT NUTRIENTS
• Plasticity,abilitytodifferentiate
• Abilitytodividecontinuously
• Immunologicalimmaturity
“Self renewal”
“Stem cell”
“Progenitor cell”
“TA cells”
“Differentiated cells”
Differen
tiation
Plu
rip
oten
cy
REPROGRAMMINGDEPROGRAMMING
CREATE THE FIRST iPS
(2007)
8
MELTON
YAMANAKA
AUGUST 2008BETA CELL NOT PRODUCING INSULIN
TO ONE THAT PRODUCES INSULIN** NO STEM CELLS **
REPROGRAMMING
Multipotent
Stem Cells Potency
Stem cell type Description Examples
Totipotent Each cell can develop into a new individual
Cells from early (1-3 days) embryos
Pluripotent Cells can form any (212) cell types
Some cells of blastocyst (5 to 14 days)
Multipotent Cells differentiated, but can form a number of other tissues
Fetal tissue, cord blood, and adult stem cells
Unipotent Cells differentiated, into one cell lines Neural Stem cells, etc..
12
EmbryoSplitting
EmbryoSplitting
6-cellembryosplitting
• EmbryonicstemcellsDerivedfromtheblastocyst,whichisaveryyoungembryoshapedlikeahollowspherethatcontains200-250cells(pre-implantationembryos)1
• AdultstemcellsMisnomer,canbefoundinchildrenandinfantstooDerivedfromtheumbilicalcordandplacenta,orfromblood,bonemarrow,skin,orothertissues
ICM
Trophectoderm
ICMisolation
culture
FeedercellshESC colony
Culture
mechanical passaging Cystic EB formation
7-10 days of culture
Gelatin-coated dishes
(endoderm) (ectoderm) (mesoderm)
AdultstemcellsUmbilicalCordIVFEmbryos
Placenta Abortedfetus
• Bonemarrow
• Peripheralblood
• Umbilicalcordblood(since1988)
• Placenta(LifebankUSA)
• PeripheralBlood
• Wharton’sjelly.
• Differentiateinto:adipocyte,chondrocytes,osteoblasts,myocytes,endothelialcells,hepatic,andnervus cells.
• Roleinregenerativemedicen.
• >13foldsinprolifertion.
• Fibroblast-like.
• Havingimmunomodulatorypotential:Applicationintreatmentofautoimmunedeseases (Rheumatoidarthriticandcrohn’s deseaseandMultiplesclerosis.
Thebloodthatisleftin
theumbilicalcordand
placentaafterthe
deliveryoftheinfant
Garbage Can
Public Banking
Private Banking
CordBlood
whattodowithit?
Option Advantages Disadvantages
The Garbage can •No cost•No headaches
•Wasting of valuable stem cells
Public cord blood banking(donation)
•Can be used by anyone in need•Increases the pool of HSC donors•Increases the pool of minority donors•No cost to the donor
•Needs public/government financial support•Not designated for the donor / family
Private cord blood collection
•Saved for own use•Future potential ??? Regenerative use ??
•Cost $$$•Will probably never be used•Socioeconomic disparity•Reducing public pool•Professional liability•Legal/ownership issues•Safety of use•Viability, duration of storage
• Richinhematopoieticstemcell.Pluripotent stemcell??
• Youngercells.Longerlifespan
• LessGVHDwhenusedforallogeniec transplant
• Immediateeasyavailability
• Lesslikelytobecontaminatedwithviruses.
• 100%Compatiblegraftforthechild.
• Notpainful.
• Couldbeusedinconjunctionwithfuturemedicaladvance.
StemCellDonorRegistriesNeedHelp!
• Bothbonemarrowandcordblooddonorsareneededworldwide.
• ArabHLAtypesareseverelyunderrepresentedonInternationalStemCellRegistries.
§ TodaytheworldregistriesarewhereUAEpatientsfindstemcelldonors.OntheInternationalRegistriesArabpopulationsare<1%.
CriteriaforDonorEligibility
1. informedconsent.
2. AbsenceoffamilyHistoryofinheriteddiseasesandnegativehistoryforHepatitisB,hepatitisCandHIVantibodies.
3. Obstetriccriteria:
1. Gestation≥34weeks.
2. Ruptureofmembranes<12hrs
3. Absenceofmaternalfeverintrapartum
4. Absenceofcongenitalabnormalities.
Insertneedleclosetocord
bloodclamp.
Gravityorsyringe.
Collectaminimumof40ml
(incl.anticoag.).
Collectiontime:2-5minutes.
Collectionofcordblood
37
41
• Dependsonkindoftwinpregnancy
• If2separatesacs,canbecollectedaftereachtwinisborn
• If1sac,collectonlyAFTERthebirthofthesecondtwin
• Mother:• HepatitisB,C
• HIV,HTLV
• CMV
• RPR.
• Antibodyscreen
• Baby:• ABO/RHtyping
• Totalnucleatedcells
• CD34+cellcount
• Bacterialandfungalcultures
• Trypan Blueviability.
• HLA
BoneMarrowQty ofharvestlarger
Engraftmentfaster
GVHR75%
Contaminationmore
Tediouscollection
Longertimetofinddonors
HLAtyping–5/6or6/6
Limitedsupply
CordbloodHarvestquantumless
Engraftmenttakeslonger
GVHR38%
Lesscontamination
Simplecollection
Donorsearchtime–halved
HLAmatch–3/6or4/6
Limitlesssupply
ü 1958 – HLA typing
ü 1988 – First reported cord blood transplant in France to curefanconi Anemia
ü 1992 – international Cord Blood transplant registry founded.
ü 1996 – First unrelated cord blood transplant at Tata MemorialHospital, Bombay.
ü 2007 – First Collection of UCB in ORIENT HOSPITSL – Syria(OCBB)
• Use of umbilical cord blood stem cells is growing everyyear.
• 30,000-40,000 transplants performedyearly worldwide.
• >20,000 patients have survived >5 years
LazarusHM.Autologousandallogeneictransplantationproceduresforhematologicmalignancies.ManualofClinicalHematology,3rdedition2002:399-409
• Cancer• Highrisk
• Relapse
• Bonemarrowfailure
• Immunodeficiency
• Hemoglobinopathy• Thalassemia
• Sicklecelldisease
• Aplastic anemia
• Metabolic/Geneticdisorders
• Autoimmunedisorders
• Cellularrepair(regenerativemedicine)?
1. Define the problem2. Find the right type of stem cell3. Match the stem cells with the
transplant recipient4. Put the stem cells in the right place5. Make the transplanted cells perform
CurrentStemCellApplications
AcuteLeukemiasAcuteBiphenotypic LeukemiaAcuteLymphocyticLeukemia(ALL)AcuteMyelogenous Leukemia(AML)AcuteUndifferentiatedLeukemiaChronicLeukemiasChronicLymphocyticLeukemia(CLL)ChronicMyelogenous Leukemia(CML)JuvenileChronicMyelogenous Leukemia(JCML)JuvenileMyelomonocytic Leukemia(JMML)Myelodysplastic SyndromesAmyloidosisChronicMyelomonocytic Leukemia(CMML)RefractoryAnemia (RA)RefractoryAnemiawithExcessBlasts(RAEB)RefractoryAnemiawithExcessBlastsinTransformation (RAEB-T)RefractoryAnemiawithRingedSideroblasts(RARS)StemCellDisordersAplasticAnemia (Severe)CongenitalCytopeniaDyskeratosis CongenitaFanconi AnemiaParoxysmal NocturnalHemoglobinuria (PNH)Myeloproliferative DisordersAcuteMyelofibrosisAgnogenic MyeloidMetaplasia(Myelofibrosis)EssentialThrombocythemiaPolycythemiaVeraLymphoproliferative DisordersHodgkin'sDiseaseNon-Hodgkin'sLymphomaProlymphocytic LeukemiaPlasmaCellDisordersMultipleMyelomaPlasmaCellLeukemiaWaldenstrom's Macroglobulinemia
nPhagocyteDisordersChediak-HigashiSyndromeChronic GranulomatousDiseaseNeutrophilActinDeficiencyReticularDysgenesisnLiposomal StorageDiseasesAdrenoleukodystrophyGaucher's DiseaseHunter'sSyndrome(MPS-II)Hurler'sSyndrome(MPS-IH)Krabbe DiseaseMaroteaux-Lamy Syndrome(MPS-VI)MetachromaticLeukodystrophyMorquio Syndrome(MPS-IV)Mucolipidosis II(I-cell Disease)Mucopolysaccharidoses (MPS)Niemann-Pick DiseaseSanfilippo Syndrome(MPS-III)Scheie Syndrome(MPS-IS)SlySyndrome,Beta-Glucuronidase Deficiency (MPS-VII)WolmanDiseaseHistiocytic DisordersFamilialErythrophagocyticLymphohistiocytosisHemophagocytosisHistiocytosis-XLangerhans'CellHistiocytosisInheritedErythrocyteAbnormalitiesBetaThalassemiaMajorBlackfan-Diamond AnemiaPureRedCellAplasiaSickleCellDiseaseCongenital(Inherited) ImmuneSystemDisordersAbsenceof T&BCellsSCIDAbsenceof TCells,NormalBCellSCIDAtaxia-TelangiectasiaBareLymphocyteSyndromeCommon VariableImmunodeficiencyDiGeorge SyndromeKostmann SyndromeLeukocyteAdhesionDeficiencyOmenn's SyndromeSevereCombinedImmunodeficiency (SCID)SCIDwithAdenosineDeaminase DeficiencyWiskott-AldrichSyndromeX-Linked Lymphoproliferative Disorder
InheritedPlateletAbnormalitiesAmegakaryocytosis /CongenitalThrombocytopeniaOtherMalignanciesBrainTumorsBreastCancerEwingSarcomaNeuroblastomaOvarianCancerRenalCellCarcinomaSmall-Cell LungCancerTesticularCancerAutoimmuneDiseasesEvanSyndromeMultipleSclerosis(Experimental)RheumatoidArthritis(Experimental)SystemicLupusErythematosus (Experimental)OtherInheritedDisordersCartilage-HairHypoplasiaCeroid LipofuscinosisCongenitalErythropoietic PorphyriaGlanzmann ThrombastheniaLesch-Nyhan SyndromeOsteopetrosisTay SachsDiseasePotentialFutureStemCellApplications*Alzheimer'sDiseaseDiabetesHeartDiseaseLiverDiseaseMuscularDystrophyParkinson'sDiseaseSpinalCordInjuryStroke
52
53
Adult cord blood stem cells injectedinto the hearts arteries are believedto improve cardiac function invictims of heart failure or heartattack.
• Regeneratespinalcord oranyothermajortissueinthebody.
• Studiesshowleukemiapatientstreatedwithstemcellsemergefreeofdisease.
• Injectionofstemcellshavealsoreducedpancreaticcancerinsomepatieents.
StemCellandDermatology
57
ParkinsonLiver cirrhosis Diabetes
FuturePotentialofStemCells
• Probablyindefinitely.Atleast10years.
Whydofamilieschoosetocollectandstoretheirbaby’scordblood?
Once– in- a- lifetimeopportunity– onlyatbirth
• Ourestimates:
(forself,forcancer):1in
2000
• CordBloodRegistryR:
• Forself:1in400
• Forotherfamily
members:1in200
It’sbettertohavethemandnotneedthem,
Thanneedthemandnothavethem.
AcknowledgementClinicalTeamS.SamawiN.KafriS.ModiM.Mousa
IVFLabJ.SharifR.DoghozA.KadriA.Konali
FetalMed.A.TahaM.KhalafM.Hazemah
Andrology LabW.HamadN.AssafM.OthmanN.MazzawiS.Sheko
Bio-Ginitic LabH.DroubiA.KhatibM.KinjA.Othman Administration
F.HamadR.QamarM.HajhasanN.OlabiE.FayadW.Saker
MedEngineeringY.KhaboriS.Khayat
AnesthesiaR.TarkoY.LakkisM.KhadraH.Sulaiman