What makes this cell special ? Plasticity, ability to differentiate Ability to divide continuously Immunological immaturity

1. Iraq - Erbil 2013
Marwan Alhalabi MD PhD
Professor in Reproductive Medicine
Faculty of Medicine
Damascus University
And
Medical Director
Orient Hospital
Assisted Reproduction Center
Damascus – Syria
Andalus University 2015

3. 1 – THE RIGHT GROWTH FACTORS
2 – THE RIGHT RECEPTORS
3 – THE RIGHT NUTRIENTS

5. • Plasticity, ability to differentiate
• Ability to divide continuously
• Immunological immaturity
“Self
renewal”
“Stem cell”
“Progenitor cell”
“TA cells”
“Differentiated cells”
Differentiation
Pluripotency

6. REPROGRAMMINGDEPROGRAMMING

8. CREATE THE
FIRST iPS
(2007)
8
MELTON
YAMANAKA
AUGUST 2008
BETA CELL NOT PRODUCING INSULIN
TO ONE THAT PRODUCES INSULIN
** NO STEM CELLS **
REPROGRAMMING

9. Multipotent
Stem
Cells
Potency

10. 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. 12

13. Embryo Splitting

14. Embryo Splitting
6-cell embryo splitting

16. • Embryonic stem cells
Derived from the blastocyst, which
is a very young embryo shaped like
a hollow sphere that contains 200-
250 cells (pre-implantation
embryos)1
• Adult stem cells
Misnomer, can be found in children
and infants too
Derived from the umbilical cord
and placenta, or from blood, bone
marrow, skin, or other tissues

17. ICM
Trophectoderm

18. ICM isolation
culture
Feeder cells
hESC colony
Culture

19. mechanical passaging Cystic EB formation
7-10 days of culture
Gelatin-coated dishes
(endoderm) (ectoderm) (mesoderm)

21. Adult stem cells Umbilical CordIVF Embryos
Placenta Aborted fetus

22. • Bone marrow
• Peripheral blood
• Umbilical cord blood
(since 1988)
• Placenta (LifebankUSA)
• Peripheral Blood

23. • Wharton’s jelly.
• Differentiate into: adipocyte,
chondrocytes, osteoblasts,
myocytes, endothelial cells,
hepatic, and nervus cells.
• Role in regenerative medicen.

24. • >13 folds in prolifertion.
• Fibroblast-like.
• Having immunomodulatory
potential: Application in
treatment of autoimmune
deseases ( Rheumatoid
arthritic and crohn’sdesease
and Multiple sclerosis.

26. The blood that is left in
the umbilical cord and
placenta after the
delivery of the infant

28. Garbage
Can
Public
Banking
Private
Banking
Cord
Blood
what to do with it?

29. 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

30. • Rich in hematopoietic stem cell. Pluripotent stem cell??
• Younger cells. Longer life span
• Less GVHD when used for allogeniec transplant
• Immediate easy availability
• Less likely to be contaminated with viruses.
• 100% Compatible graft for the child.
• Not painful.
• Could be used in conjunction with future medical advance.

31. Stem Cell Donor Registries Need Help!
• Both bone marrow and cord blood donors are needed world
wide.
• Arab HLA types are severely under represented on
International Stem Cell Registries.
§ Today the world registries are where UAE patients find
stem cell donors. On the International Registries Arab
populations are <1%.

32. Criteria for Donor Eligibility
1. informed consent.
2. Absence of family History of inherited diseases and
negative history for Hepatitis B, hepatitis C and HIV
antibodies.
3. Obstetric criteria:
1. Gestation ≥ 34 weeks.
2. Rupture of membranes < 12 hrs
3. Absence of maternal fever intrapartum
4. Absence of congenital abnormalities .

33. Insert needle close to cord
blood clamp.
Gravity or syringe.
Collect a minimum of 40ml
(incl. anticoag.).
Collection time: 2-5 minutes.
Collection of cord blood

37. 37

41. 41

42. • Depends on kind of twin
pregnancy
• If 2 separate sacs, can be
collected after each twin
is born
• If 1 sac, collect only
AFTER the birth of the
second twin

43. • Mother:
• Hepatitis B,C
• HIV, HTLV
• CMV
• RPR.
• Antibody screen
• Baby:
• ABO/RH typing
• Total nucleated cells
• CD34+ cell count
• Bacterial and fungal cultures
• Trypan Blue viability.
• HLA

44. Bone Marrow
Qty of harvest larger
Engraftment faster
GVHR 75%
Contamination more
Tedious collection
Longer time to find donors
HLA typing –5/6 or 6/6
Limited supply
Cord blood
Harvest quantum less
Engraftment takes longer
GVHR 38%
Less contamination
Simple collection
Donor search time –halved
HLA match –3/6 or 4/6
Limitless supply

45. ü 1958 – HLA typing
ü 1988 – First reported cord blood transplant in France to cure
fanconi Anemia
ü 1992 – international Cord Blood transplant registry founded.
ü 1996 – First unrelated cord blood transplant at Tata Memorial
Hospital, Bombay.
ü 2007 – First Collection of UCB in ORIENT HOSPITSL – Syria
(OCBB)

46. • Use of umbilical cord blood stem cells is growing every
year.
• 30,000-40,000 transplants performedyearly worldwide.
• >20,000 patients have survived >5 years
Lazarus HM. Autologous and
allogeneic transplantation
procedures for hematologic
malignancies. Manual of
Clinical Hematology, 3rd
edition 2002:399-409

47. • Cancer
• High risk
• Relapse
• Bone marrow failure
• Immunodeficiency
• Hemoglobinopathy
• Thalassemia
• Sickle cell disease
• Aplastic anemia
• Metabolic/Genetic disorders
• Autoimmune disorders
• Cellular repair (regenerative
medicine)?

48. 1. Define the problem
2. Find the right type of stem cell
3. Match the stem cells with the
transplant recipient
4. Put the stem cells in the right place
5. Make the transplanted cells perform

51. Current Stem Cell Applications
Acute Leukemias
Acute Biphenotypic Leukemia
Acute Lymphocytic Leukemia (ALL)
Acute Myelogenous Leukemia (AML)
Acute Undifferentiated Leukemia
Chronic Leukemias
Chronic Lymphocytic Leukemia (CLL)
Chronic Myelogenous Leukemia (CML)
Juvenile Chronic Myelogenous Leukemia
(JCML)
Juvenile Myelomonocytic Leukemia (JMML)
Myelodysplastic Syndromes
Amyloidosis
Chronic Myelomonocytic Leukemia (CMML)
Refractory Anemia (RA)
Refractory Anemia with Excess Blasts (RAEB)
Refractory Anemia with Excess Blasts in
Transformation (RAEB-T)
Refractory Anemia with Ringed Sideroblasts
(RARS)
Stem Cell Disorders
Aplastic Anemia (Severe)
Congenital Cytopenia
Dyskeratosis Congenita
Fanconi Anemia
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Myeloproliferative Disorders
Acute Myelofibrosis
Agnogenic Myeloid Metaplasia
(Myelofibrosis)
Essential Thrombocythemia
Polycythemia Vera
Lymphoproliferative Disorders
Hodgkin's Disease
Non-Hodgkin's Lymphoma
Prolymphocytic Leukemia
Plasma Cell Disorders
Multiple Myeloma
Plasma Cell Leukemia
Waldenstrom's Macroglobulinemia
nPhagocyte Disorders
Chediak-Higashi Syndrome
Chronic Granulomatous Disease
Neutrophil Actin Deficiency
Reticular Dysgenesis
nLiposomal Storage Diseases
Adrenoleukodystrophy
Gaucher's Disease
Hunter's Syndrome (MPS-II)
Hurler's Syndrome (MPS-IH)
Krabbe Disease
Maroteaux-Lamy Syndrome (MPS-VI)
Metachromatic Leukodystrophy
Morquio Syndrome (MPS-IV)
Mucolipidosis II (I-cell Disease)
Mucopolysaccharidoses (MPS)
Niemann-Pick DiseaseSanfilippo Syndrome (MPS-III)
Scheie Syndrome (MPS-IS)
Sly Syndrome, Beta-Glucuronidase Deficiency (MPS-VII)
Wolman Disease
Histiocytic Disorders
Familial Erythrophagocytic
Lymphohistiocytosis
Hemophagocytosis
Histiocytosis-X
Langerhans' Cell Histiocytosis
Inherited Erythrocyte Abnormalities
Beta Thalassemia Major
Blackfan-Diamond Anemia
Pure Red Cell Aplasia
Sickle Cell Disease
Congenital (Inherited) Immune System Disorders
Absence of T & B Cells SCID
Absence of T Cells, Normal B Cell SCID
Ataxia-Telangiectasia
Bare Lymphocyte Syndrome
Common Variable Immunodeficiency
DiGeorge Syndrome
Kostmann Syndrome
Leukocyte Adhesion Deficiency
Omenn's Syndrome
Severe Combined Immunodeficiency (SCID)
SCID with Adenosine Deaminase Deficiency
Wiskott-Aldrich Syndrome
X-Linked Lymphoproliferative Disorder
Inherited Platelet Abnormalities
Amegakaryocytosis / Congenital
Thrombocytopenia
Other Malignancies
Brain Tumors
Breast Cancer
Ewing Sarcoma
Neuroblastoma
Ovarian Cancer
Renal Cell Carcinoma
Small-Cell Lung Cancer
Testicular Cancer
Autoimmune Diseases
Evan Syndrome
Multiple Sclerosis (Experimental)
Rheumatoid Arthritis (Experimental)
Systemic Lupus Erythematosus (Experimental)
Other Inherited Disorders
Cartilage-Hair Hypoplasia
Ceroid Lipofuscinosis
Congenital Erythropoietic Porphyria
Glanzmann Thrombasthenia
Lesch-Nyhan Syndrome
Osteopetrosis
Tay Sachs Disease
Potential Future Stem Cell Applications*
Alzheimer's Disease
Diabetes
Heart Disease
Liver Disease
Muscular Dystrophy
Parkinson's Disease
Spinal Cord Injury
Stroke

52. 52

53. 53

54. Adult cord blood stem cells injected
into the hearts arteries are believed
to improve cardiac function in
victims of heart failure or heart
attack.

55. • Regenerate spinal cord or any other major
tissue in the body.

56. • Studies show leukemia patients treated with stem cells
emerge free of disease.
• Injection of stem cells have also reduced pancreatic
cancer in some patieents.

57. Stem Cell and Dermatology
57

58. ParkinsonLiver cirrhosis Diabetes

59. Future Potential of Stem Cells

60. • Probably indefinitely. At least 10 years.

61. Why do families choose to collect and
store their baby’s cord blood?
Once – in- a- lifetime opportunity – only at birth

62. • Our estimates :
(for self, for cancer): 1 in
2000
• Cord Blood RegistryR:
• For self: 1 in 400
• For other family
members: 1 in 200

63. It’s better to have them and
not need them ,
Than need them and not have
them .

65. Acknowledgement
Clinical Team
S. Samawi
N. Kafri
S. Modi
M. Mousa
IVF Lab
J. Sharif
R. Doghoz
A. Kadri
A. Konali
Fetal Med.
A. Taha
M. Khalaf
M. Hazemah
Andrology Lab
W. Hamad
N. Assaf
M. Othman
N. Mazzawi
S. Sheko
Bio-Ginitic Lab
H. Droubi
A. Khatib
M. Kinj
A. Othman Administration
F. Hamad
R. Qamar
M. Haj hasan
N. Olabi
E. Fayad
W. Saker
Med Engineering
Y. Khabori
S. Khayat
Anesthesia
R. Tarko
Y. Lakkis
M. Khadra
H. Sulaiman