cord blood stem cells

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..

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

• 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

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

cord blood stem cells

Health & Medicine