Public cord blood banking

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Public cord blood banking
Spring 2009
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In 1988, the first umbilical cord blood
transplantation (CBT) was reported by Prof
Gluckman in a child with Fanconis anemia,using
cord blood (CB) from his HLA matched sister.

• It tooks another 7 years until the first CBT was
  performed in an adult recipient.
• To date nearly 14,000 of umbilical cord blood
  transplants have been performed worldwide in
  pediatric and adult patients.
• more than 95 of patients who are in need for
  transplantation are able to find 46/6 matched
  unit in CB registries, according to NetCord or
  National Marrow Donor Program (NMDP) report.

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• source of stem cells
• The stem cells used in most transplants today
  come from BM.
• BM transplants have been performed successfully
  since 1969, nearly 20 years before the first
  successful cord blood transplant.Stem cells are
  also found in
• Blood circulating in the body
• Fat obtained during liposuction
• Muscle
• Bone
• Skin
• Blood Vessels
• Brain
• Gastrointestinal tract
• Retina
• Liver
• Pancreas
• Cornea
• human embryos
• fetal tissue
• hair follicles

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Characterization of Hematopoietic Stem Cell

• Surface marker
• CD34
• CD 38
• HLA-DR
• c-Kit
• Thy-1 (CD90)
• Lin (Glycophorin, Trasferin receptor,CD33, CD15,
  CD20,CD3,CD45RA,CD41)
• Dye exclusion
• Rhodamine-123/low, Hoechst-33342/low
• ATP-binding cassette (ABC) transporters
• Multidrug Resistance P-glycoprotein (MDR1)
• Breast Cancer-Resistance Protein (BCRP)
• In vitro culture

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• Advantages of bone marrow
•  Producing new cells in about 18 days, one to two
  weeks faster than cord blood transplants.
• Bone marrow can be used to treat patients of any
  size, one log more cells.
• More than one unit of bone marrow can be
  collected from the same donor.
• Advantages of Cord blood
• Easily and rapidly available UCB unit averages 2
  weeks, compared with 2 months for BM.
• Absence of risk for mother and newborn and its
  painless and no side effects.
• Lower risk of GVHD (low number naïve repertoire
  of CB-derived T cells )
• Lower risk of infection contamination
  particularly CMV
• Preserved GVL effect (higher number unique
  property of NK cells in CB)
• The comparison of the gene expression profiles of
  PB, BM,CB HSCs suggests the potential to
  differentiate into no hematopoietic lineages
• CB HSCs express special TF not seen in HSCs from
  other sources, inhibit differentiation and
  higher proliferation

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• Cord blood banking
• is a procedure in which the umbilical cord blood
  after birth is
• Collected
• Shipped
• Processed
• Frozen
• Stored (in private or public banks) and
• Release for future medical use.
• Cord blood is enriched source of primitive
  stem/progenitor cells
• The building blocks of the blood and immune
  system
• Ability to differentiate into other tissues,
  organs, and blood vessels
• To treat a host of diseases.
• Hematopoietic stem cell transplantation, after
  high-dose chemoradiotherapy

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• CBU Collection
• In collection bags containing 25ml of CPD
  anticoagulant in-utero and/or ex-utero methods.
  Products were stored hours prior to processing.
• CBU Processing
• Pre-processing cell count.
• Hydroxyethylstarch (HES)-at 20 v/v.
• Buffy coat fraction
• Recover into collection bag
• Cells in final product prior to cryopreservation
  for
• Nucleated cell count (WBCNRBC)
• Viability (PI)
• Flow cytometry(CD45 dim CD34 enumeration)
• CFU assay
• Cells were plated in duplicate at concentration
  of 5 X 104/mL per plate using Methocult complete
  media. BFU-E, CFU-GM or CFU-GEMM colonies were
  enumerated after 14 days.

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Kinds of banking on cord blood Public cord blood
banks The first public banking on unrelated UCBB
was started in New York in 1993. About 225,000 CB
units frozen in 38 public cord banks in 25
countries.Donating is free. Private cord blood
banks The first private banking began 15 years
ago. For autologous or related allogeneic
transplantation, but this issue raises growing
scientific and ethical criticism.Donating isnt
free. Saved for a family member who has a
medical need For a biological sibling or parent
has a disease for directed donation. Used for
research studies by a laboratory or technology
company. To improve the transplant process for
future patients To new therapies using cord
blood. Based on the last Eurocord report out of
3,372 umbilical cord transplants in 19882007,
done in 43 countries at 373 transplant centers,
2965 were unrelated donors, 359 were related but
only three were autologous.
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• Public versus private
• ? The individuals chances of using cord blood
  for hematopoietic disorders before 20 years is
  low from 1/20000 to 37/100000.
• However, it is not clear how many of those 37
  peoples can use autologous sources.
• ? There are alternatives to directed CBB for
  those who require transplantation through NetCord
  or NMDP
• ? Own cells may be inappropriate in conditions
  where the disease has a genetic origin, such as
  some leukemia.
• As a result, autologous commercial storage is
  unlawful in some European states.
• In 2004, the European Group on Ethics in Science
  and New Technologies advised that
• they sell a service, which has presently, no real
  use regarding therapeutic options.
• Thus they promise more than they can deliver.
• The activities of such banks raise serious
  ethical criticisms
• The Group did not go recommending banning this
  activity but also recommended that
• any kind of advertising made by commercial cord
  blood banks in the media, including on the
  Internet, must be adequately controlled by public
  authorities.

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Why public banking is limited

• The US private cord blood bank sales a cost of
  4070 for UCB collection and storage for 20
  years.In sensitivity analysis, if the cost of
  cord blood is lt201 or if needing a stem cell
  transplant is gt1/125, private cord blood banking
  becomes cost-effective.Private cord blood
  banking is only cost effective for families in
  which the children have a known diagnosis and
  needing a stem cell transplant
• In order to accept donations for free, the bank
  must have income to support the laboratory.
• That income may come from
• 1-Federal support
• 2-Profit margin of private banking
• 3-Selling some of the donations to research
  programs
• 4-Combination of the above

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• In Canada, the Fetal Medicine Committee of the
  Society of Obstetrician and Gynaecologists
  recommended that
• establish registration, regulation and
  accreditation of CBB should be carefully
  regulated.
• In the USA, on the recommendation of the
  Institute of Medicine of the National Academies,
  Congress voted US77 million for the
  establishment of a National Cord Blood Stem Cell
  Bank.
• The RCOG strongly supports of a National CBB for
  allogeneic storage.
• In early 2007, AAP, discourages families from
  thinking of private storage as "biological
  insurance,".
• Instead,encourages private cord blood banking
  when a sibling in the family has a medical
  condition such as leukemia, lymphoma, aplastic
  anemia.

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• Although there are few organizations (FDA, NMDP,
  FAHCT/NetCord, AABB) work on quality of CB units
  registered for transplantation,
• there are still few challenges between different
  banks on Processing, testing and freezing of
  successfully collected CB because of loss in
  initially harvested blood volume and cell dose.
• To promote international standards for CBB
• To provide unified access to high quality cord
  blood units from member banks.
• NETCORD collaborated with FACT to establish the
  NETCORD-FACT Standards for Cord Blood Banks
• Dr. Pablo Rubinstein, the NYBC's National Cord
  Blood Program Director president of NETCORD
  estimates that about 14,000 cord blood
  transplants have been performed worldwide.

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Examples of organizations offering
accreditation, on an international level, related
to registry operations(APRIL 2008)
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Informed Consent for Cord Blood Donors

• In order to be a transplant donor, the mother
  must pass a blood test for the following
  infectious agents within 7 days of delivery
• Human Immunodeficiency Virus (HIV), type 1
• Human Immunodeficiency Virus (HIV), type 2
• Hepatitus B virus
• Hepatitus C virus
• Human T-cell lymphotropic virus, type I
• Human T-cell lymphotropic virus, type II
• Treponema pallidum (Syphilis)
• CytoMegaloVirus (CMV) (unless previously
  documented positive)
• In order to be suitable for transplant, the cord
  blood collection must pass a blood test for
  contamination (by bacteria or spores in the
  delivery room) and is then typed for
• ABO group and Rh type
• HLA-A, -B, and -DR antigens
• Hemoglobin electrophoresis in ethnic groups at
  high risk for hemoglobinopathies The above
  guidelines were published in 2003 by the
  International Society for Cellular Therapy
  (ISCT), based on a multi-organization
  collaboration, including
• American Association of Blood Banks (AABB)
• America's Blood Centers
• American Red Cross (ARC)
• American Society for Blood and Marrow
  Transplantation
• Foundation for the Accreditation of Cellular
  Therapy (FACT)
• National Marrow Donor Program (NMDP)

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Summary of chronological aspects of the clinical
use of cord blood 1988- First Cord blood
transplant.1989-92-Clinical observation that
GvHD was reduced even in HLA incompatible
CBT. 1992-1993-Establishment of Cord Blood
Banks.(New York,Paris,Milan and
düsseldorf)  1993-1996-Feasibility of unrelated
mismatched CBT represent real alternative to
gold standard matched BMT.1995-Establishment
of Euro cord group program sponsored by European
Union.1997-Nucleated cell and CD34dose are more
important factor for engraftment and survival
(Eurocord group study).1998-Large series of UCBT
confirmation of the impact of cell dose and
HLA.1998-Foundation of the NETCORD organization
in order to control the quality of cord blood
units.2000-Retrospective comparisons between
UBMT and UCBT.2002-Use of cord blood cells in
adults with promising results.2003-Criteria of
cord blood choice and indications.2004-Use of
double CBT and reduced intensity conditioning in
adults.2004-Isolation of USSC from umbilical
cord blood.2004-Comparable results between
unrelated CBT and UBMT in adults.2005-Exvivo
expansion of UCB-derived Stem cells2006-co-transp
lantation of CB with limited no of HSC from
haploidentical sibling.2007-2008- Intra-bone
graft injection due to better SC homing,recovery
23-36 days
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• Our happy parents are always reminded to write in
  their babys book the following
• Your first act of charity was to give life to
  someone else.

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• What diseases can be treated with cord blood?
• More than 70 different diseases including
• Leukemia
• Immune deficiency
• Sickle cell anemia
• Aplastic anemia
• Thalassemia
• Lymphomas such as Hodgkin's disease and
  non-Hodgkin's lymphoma, and similar diseases with
  genetic basis but lesser-known conditions.
• Promising new research indicates to treat people
  with
• Diabetes
• Spinal-cord injuries
• Heart failure
• Stroke
• Neurological disorders such as multiple
  sclerosis.
• Most of these studies have been performed on
  animals, however, and the results are much more
  preliminary, say some experts, than the public
  has been led to believe.