1. H A Y WO O D L . B R O WN , M D
R O Y T . P A R K E R P R O F E S S O R A N D C H A I R
D U K E U N I V E R S I T Y
J U N E 2 0 1 3
UMBILICAL CORD BLOOD DONATION
IMPLICATIONS FOR THE OBSTETRICIAN

3. HISTORY OF STEM CELL RESEARCH
• 1960’s
• Researchers discover bone marrow contains two types of
cells
• hematopoietic stem cells – forms all
types of blood cells
• Bone marrow stromal cells – mixed cells
that generate bone, cartilage, fat,
fibrous connective tissue

4. STEM CELL RESEARCH
• 2000’s
• Stem cell research gets “political” primarily as a result of the
sources for obtaining embryonic stem cells and their use.
• Politics and Stem cell – Abortion controversy

5. CORD BLOOD LEGISLATION
• 2005 – CW Bill Young Transplantation Program, the
Stem Cell Therapeutic and Research Act of 2005
created the National Cord Blood Inventory (NCBI)
with the goal of increasing the national supply of
publicly donated cord blood units

6. STEM CELLS
• What are Stem Cells (Properties)
• Capable of dividing and renewing themselves for long
periods
• Unspecialized
• Can give rise to specialized cell types

7. PATIENT KNOWLEDGE OF
CORD BLOOD BANKING
• Perlow. J reprod med 2006;51:642-648
• Survey of 425 patients
• Older patients with higher education more knowledgeable
• Greatest disparity of knowledge among Native Americans
• 50% were misinformed that UCBB was only for “the child that I
will deliver.”
• Only 14% of patients were educated about UCBB by nurse or
obstetrician.

8. AWARENESS OF UCBB
PERLOW 2006
• Education % p
• < 8th grade 21.9 <0.00001 vs. all levels
• High School 59.1 0.039 HS vs. College
• College degree 70.6
• Graduate degree 77.6 0.021 HS vs. Graduate
• Race/Ethnicity
• Caucasian 73.8 <0.0001 vs. All races
• Hispanic 43.2 <0.0001 vs. Caucasian
• African American 48 <0.001 vs. Caucasian
• Native American25 <0.0001 vs. Caucasian
• Asian 50 NS

9. UMBILICAL CORD BLOOD BANKING
• Perlow. J Reprod Med 2006
• If physicians are unaware of the benefits of UCBB and/or
not informing patients of their options in this regard,…
potential therapeutic options can be missed

10. NORTH CAROLINA CORD BLOOD
EDUCATION LEGISLATION
• North Carolina
Jun 9, 2009 ... North Carolina Governor Beverly Perdue signs
cord blood education legislation
• The Department of Health and Human Services shall make online
materials available and will encourage healthcare professionals to
educate all pregnant patients on their cord blood options, to ensure
every family has the opportunity to make an informed choice.
• The law also encourages physicians to make the information
available to expectant parents early enough in the pregnancy
so that they can make an informed decision about whether to
participate in a public or private cord blood banking program.

11. STATES WITH CORD BLOOD
LEGISLATION

12. BIPARTISAN LEGISLATION PROMOTING
LIFE-SAVING MEDICAL ADVANCES
CLEARS SENATE
• The Stem Cell Therapeutic and Research
Reauthorization Act of 2010 (S. 3751), unanimously
approved by the Senate today, reauthorizes the original
2005 act and extends the C.W. Bill Young Cell
Transplantation and National Cord Blood Inventory
(NCBI) programs through Fiscal Year 2015.

13. ACOG COMMITTEE OPINION
# 399. FEBRUARY 2008
• Recommendations (Information to Patient)
• balanced and accurate information on advantages and
disadvantages of public vs. private
• Remote chance of autologous unit being used of 1 in 2700
individuals
• Disclosure that demographic data will be maintained,
maternal infectious disease and genetic testing, ultimate
outcome of poor quality units
• Provider not obligated to obtain consent for private
banking
• Collection should not alter routine delivery practices
• Disclose any financial and conflict of interest for for-profit
UCBB

14. STEM CELLS
• Embryonic Stem Cells
• Derived from four to five day old embryos
• Adult Stem Cells
• Undifferentiated cells found among differentiated cells in a
tissue or organ

15. EMBRYONIC STEM CELLS
Human Embryonic Stem Cells
• Obtained from donated embryos that have
developed from eggs fertilized in vitro (in the lab)
• Potentially unlimited capacity to replenish
themselves and are pluripotent, meaning that they
can differentiate into any cell type found in the
adult body.
• Embryonic stem cell therapies have been proposed
for regenerative medicine and tissue replacement
after injury or disease.

16. STEM CELLS
• Embryonic
• Blastocysts cells
• Isolated in the laboratory by transferring inner cell mass into
tissue culture
• Inner cell mass proliferates and divides and are replated
(subculture)
• Over six months the original 30 cells become millions of
undifferentiated embryonic stem cells that are pluripotent

17. CORD BLOOD STEM CELLS
• Cord blood contains embryonic-like stem cells.
• Cord blood stem cell is not quite as primitive as the
controversial embryonic stem cells, which can give
rise to any tissue type of the body.
• CB cells are more versatile than adult stem cells
such as those found in bone marrow.

18. ADULT STEM CELLS
• An adult stem cell is an undifferentiated cell found
in a tissue or organ.
• Produces more stem cells and can also give rise to
specialized cell types of the tissue or organ they are
located in.
• The main job of an adult stem cell is to maintain
and repair the tissue in which it is found.
• When compared to embryonic and cord blood
stem cell, adult stem cells are believed to be more
limited in the type of cells that they can generate.

19. ADULT STEM CELLS
• Adult (somatic) stem cells
• An undifferentiated cell found among differentiated cells in
a tissue or organ
• Can renew itself
• Can differentiate to yield specialized cell types
• Role is to maintain and repair tissue in a living organism
• Origin in mature tissue is unknown
• Growing adult stem cells from culture can be challenging

20. STEM CELLS
• Primary Differences in Embryonic and Adult Stem
Cells
• PROLIFERATION
• Embryonic stem cells can proliferate
without differentiating but adult stem
cells cannot.

21. STEM CELL TRANSPLANTATION
• National Bone Marrow Donor Program
• 5.5 million adult donors
• Unrelated donor matching uses low resolution typing in the
80% race for whites, Hispanics and Asians.
• African American matches only around 60%
• Affiliated with 15 umbilical cord blood banks with inventory
of over 40,000 units.
• In 1999, NBMDP established network of banks listing their units on
the NMDP Registry and the Center for Cord Blood in 2005

22. BONE MARROW DONOR MATCHING BY RACE
• Likelihood of finding a donor
• African American – 66%
• Hispanic or Latino – 72%
• Asian and Pacific Islander – 82%
• White – 93%

23. CORD BLOOD FOR TRANSPLANTATION
• Hematopoietic progenitor (stem) cells from cord
blood have advantages over bone marrow
• Unlimited supply
• Ethnic diversity easier to achieve
• Painless collection
• Higher proliferative capacity
• Lower rate of acute graft vs. host disease (a greater HLA
mismatch is better tolerated)
• No donor attrition as with bone marrow

24. ADVANTAGES OF CORD BLOOD
• Biologically, a greater degree of human leukocyte
antigen mismatch between the donor and
recipient is tolerated by patients, allowing more
patients, including those from diverse racial and
ethnic background, to receive a cord blood
transplant
• Relevant to African Americans
• The incidence of acute and chronic graft versus
host disease is decreased with UCBD
• Cord blood is stored and readily available for those
needing transplantation.

25. CORD BLOOD TRANSPLANTATION
• Compared to Bone marrow
• CD 34+ cells have higher rate of proliferation
• Greatest limitation is lower total nucleated cells or CD 34+
count
• Lower number of CD 34+ leads to longer interval for
neutrophil and platelet recovery
• Signs of engraftment
• Transplanted cell dose ~ 10% of marrow transplants
• CD8+ lymphocytes is reduced in cord blood leading to less
graft vs. host

26. CORD BLOOD TRANSPLANTATION
• Cord blood progenitor cells and lymphocytes subsets
in cord blood influenced by:
• # of nucleated red cells
• Greater CD34+ with higher nucleation
• Caucasian ethnicity
• Higher CD3+/CD38- in Caucasians than AA, Asians
• Infant Gender
• Male infants have fewer CD3+/CD4+, C19+ but higher CD3+/CD8+
• Type of delivery
• Higher # of total CFU’s with cesarean delivery but lower
CD3+/CD4+, CD3=/CD8+, and CD 19+

27. CORD BLOOD TRANSPLANTATION
• Disadvantages
• Inability to obtain additional cells for second transplant
• Small volumes
• Slower engraftment

28. CORD BLOOD TRANSPLANTATION
• Disadvantages
• Studies underway to evaluate methods to overcome limited
cell dose
• Combining two or more closely matched cord blood units
• Co-infusion of mesenchymal cells or
• Ex vivo expansion of the cells

29. CORD BLOOD TRANSFUSION

30. CORD BLOOD TRANSFUSION
• CIBMTR data
• Lifetime probability of undergoing a transplant with one’s
own hematopoietic stem cells in US from marrow, peripheral
blood and cord blood
• 1 in 400 if the indications for autologous HSCT do not change
• Nietfield JJ. Biol blood Marrow Transplant, 2-8,14:316-322

31. CORD BLOOD TRANSFUSION

32. CORD BLOOD BANKING
• Types of Cord Blood Banks
• Private Banking
• Public Banking
• Directed Donor Banks

33. CORD BLOOD BANKING
• Private Banking
• Direct patient advertising and recruitment
• “Biology insurance”
• College savings plans
• Discounts for second and third child

34. CORD BLOOD BANKING
• Private Banking
• Over 24 private banks in the U. S.
• Collected on site by obstetrician for
autologous use Limited testing for
infectious diseases
• Initial HLA typing not performed
• Initial fees $1100 - $1750 with yearly fees
for storage of $115 - $125
• If used processing and shipment fees
paid by insurance (OB $$$$ for
collection)

35. CORD BLOOD TRANSPLANTATION
• Realities for chances of need and use
• For majority of blood cancers and blood diseases, an
autologous unit would not be used if the donor ultimately
needed a transplant because the disease may be present
in the cord blood cells
• The best source of cells for a transplant is from a fully
matched sibling, or if unavailable, an unrelated donor
(allogeneic transplant)

36. CORD BLOOD BANKING
• Private Banking
• ACOG Committee Opinion
• “Parents should not be sold this service without
a realistic assessment of their likelihood of return
on investment”
• Cord blood stem cells survive after freezing for up
to ~ 15 years

37. CORD BLOOD BANKING
• Some public banks will accepts units from any
provider through shipment by an overnight express
courier

38. CORD BLOOD TRANSPLANTATION
• Private Banking
• Legal concerns for the obstetrician
• Liability for collection of poor quality units if later required for
transfusion
• Patent infringement
• Public Banking
• Greater access by the general public
• More cost effective
• Will accept patient donations

39. CORD BLOOD TRANSPLANTATION
• Used in both children and adults
• Limited amount of blood forming cells
• Smaller patients need fewer cells
• Larger patients need combined cord blood units
• Emerging technology
• Laboratory methods to grow the number of cells before
transplanting

40. INDICATIONS FOR TRANSPLANTATION
• Malignant Hematopoietic Diseases
• Acute leukemia: Lymphoblastic or myelogenous
• Hodgkin’s lymphoma and non-Hodgkin’s lymphoma
• Chronic myelogenous leukemia
• Nonmalignant/Heriditary Hematopoietic
• Sickle cell anemia and thalassemia
• Fanconi’ Anemia
• Chronic granulomatous disease
• Severe congenital neutropenia

41. INDICATIONS FOR TRANSPLANTATION
• Emerging Indications
• Neurological injuries, including cerebral palsy
• Type 1 insulin-dependent diabetes mellitus

42. UMBILICAL CORD BLOOD
TRANSPLANT

43. UCB AND HURLER’S SYNDROME
• Hurler’s
• Inherited metabolic disease with lack of enzyme lysosomal
α-L-iduronidase
• Cord blood increases the level of lysosomal a-L-iduronidase

44. CORD BLOOD TRANSPLANTATION
• Hurler’s Syndrome
• 258 infants and children from age 2 mo-18years (median
age 16 mo) of which ½ received unrelated cord blood
transplants (81% from mismatched donors)
• Higher rate of donor cell engraftment (complete replacement
of bone marrow with donor cells), normal enzyme levels than
those of matched sibling cells or matched/unmatched bone
marrow
• 98% of UCB recipients with successful engraftment had normal
enzyme levels
• Boelens et al. Blood, 2013

45. CORD BLOOD TRANSPLANTATION
• Case Report
• Treatment of Krabbe Disease (Globoid Cell Leukodystrophy)
with cord blood transplantation.
• Krabbe Disease
• Progressive cerebral degenerative disease
• Clinical onset before 6 months of age with death by age 2 years
• Autosomal recessive with carrier testing and prenatal diagnosis
availability

46. CORD BLOOD TRANSPLANTATION
• Krabbe Disease
• McGraw et al. Radiology 2005;236:221
• 15 newborns with transplantation for
Krabbe disease
• Normal myelination and neurological
development after transplantation

47. CORD BLOOD TRANSPLANTATION
• Ongoing Research for Cord Blood Use
• Birth Asphyxia
• Transfusion could lead to regeneration of damaged neural
tissue
• Stroke
• Transplantation enhance recovery from stroke
• Myocardial damage after MI
• Transplantation may enhance healing of heart
• Genetic Predisposition to chronic disease
• Transplantation possible prevent onset

48. CORD BLOOD TRANSPLANTATION
NEURAL CONDITIONS
• Case Report
• Treatment of infant with severe hydrocephaly from
aqueductal stenosis
• Implications for regeneration of neural tissue

49. CORD BLOOD TRANSPLANTATION
• Cerebral palsy
• 1 in 500 children in US diagnosed annually
• No known treatment
• Therapeutic benefits of UCB stem cell trans-fusion using
autologous blood being studied at Duke University.

50. CORD BLOOD TRANSPLANTATION
FUTURE DIRECTIONS
• Prevention of Atherosclerosis
• Progenitor cell-based therapy to prevent or cure
established disease
• Reserve the health consequences of atherosclerosis
in adults
• Immune ablation required for transplantation poses
certain risk
• Ethical issues for human trials for those without
obvious injury
*Working Group on Ethics of Progenitor Cell base
strategies for disease prevention

51. CORD BLOOD BANKING
IMPLICATIONS FOR PROVIDERS
• Be informed about potential for transplantation and
indications for collection
• A sibling or parent in need of stem cell transplantation
when HLA identical bone marrow or stem cell
donation from a sibling or parent is unavailable

52. CORD BLOOD BANKING
IMPLICATIONS FOR PROVIDERS
• Allogeneic transplantation is treatment of choice
for a child with no HLA –identical sibling or donor
• Allogeneic transplantation in young adults with
hematologic malignancies in urgent need of
transplantation
• Altruistic donation for public banking for allogeneic
transplantation

53. CORD BLOOD BANKING
IMPLICATIONS FOR PROVIDERS
• “Safe management of obstetric delivery should
never be compromised to facilitated cord blood
collection”
Armson BA. J Obstet Gynaecol Can 2005,3:263

54. SUMMARY
• Advantages
• Abundantly available
• No ethical concerns (i.e. embryonic )
• Ethnic balance
• Low viral contamination with CMV and EB virus
• Cryoperserved, banked and available on demand
• No observed malignant transformation of UCB observed
• Undistorted accumulation of HLA genotypes because stored
UCB has no attrition except use
• Frozen UCB easily shipped, thawed and used

55. THE BOOZER’S FAMILY STORY
• Twins, who do not have sickle cell disease,
presented a chance of a cure for their brother.
Using umbilical cord blood from the twins, 17-
month-old Carmani underwent a successful stem
cell transplant.