Cord blood and stem cells
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Transcript of Cord blood and stem cells
Cord blood storage and stem cells
Keith Tsui
Outline
• Introduction• The state of cord blood in HK• Existing clinical applications• Potential therapies
Umbilical cord and stem cellsCord Blood Cord Tissue
Stem cells Hematopoietic stem cells Mesenchymal stem cellsCurrent treatments
Hematological, immunological and metabolic storage disorders
No
Storage Availability
Public and private Private only
Future potential Ex vivo expansion for adult useGene therapy?
Regenerative therapy?
Hong Kong
• Public– Hong Kong Red Cross (since 1998)– KWH only due to logistic reasons
• Private– Healthybaby– Cordlife– Cryolife
Public vs Private
• Public:– Allogenic donation
• Private:– Autologous use– Estimated 1 in 2700 to 1 in 20000 chance of cord
blood being used by family member or child– Cost of initial processing and annual storage fee
Sources of cord blood storageNon-directed Directed
Low risk
Donations, public “insurance?”, private
At risk Donations, public “savior sibling”, public/ private
QMH guideline1. Routine directed commercial cord blood collection and stem-
cell storage is not recommended at the present time because of insufficient scientific base to support such practice. Parents’ request should be refused because of logistic problems of collection of cord blood (for private banking) in H.A. hospitals.
2. Collection of cord blood for directed donations for at risk families (e.g. for siblings with β thalassaemia major) should be arranged with the prenatal diagnosis team. The mother requesting collection for directed donations should be referred to PDC for counselling if she is not a patient of the PDC.
How to collect?• When?During third stage or shortly thereafter
• Always focus on minimizing adverse neonatal outcome and postpartum hemorrhage first, Especially if there is prematurity, nuchal cord, C-section, multiple pregnancy
• RCOG recommendation: – There should be no alteration in usual management of the third stage– Collection should be made from the ex utero separated placenta– Collection should be by a trained technician (not midwife or obstetrician)
licensed by the Human Tissue Authority – Service should not be made available when attending clinician believes it to
be contraindicated (nuchal cord or maternal hemorrhage)
Procedure for ex utero collection• Placenta suspended from collection stand• Cord cleansed with antiseptic solution• 16 gauge needle inserted into umbilical vein• Blood allowed to drain into collection bag
with anticoagulant by gravity• Until cord appears empty and mostly white
usually after 2-4 minutes• Volume below 40ml is unlikely to be
sufficient
Follow up studies• Cord blood units should be tested, processed and stored
within 48 hours– Unit volume, weight, total nucleated cell count with differential,
hematopoietic potential (CD34+ cell count or colony forming unit)– ABO/Rh blood type, HLA class I and class II haplotypes– HBV, HCV, HIV, syphilis, CMV, bacterial culture– Hb electrophoresis
• Maternal blood sampling within 7 days for infection screen and maternal HLA type
• Shelf-life: retained viability and engraftment potential for >10 years
History of cord blood transplant
• First case in 1988 for Fanconi anemia• Estimated more than 7000 transplants done
up to 2008• Since 1998, 20% of stem cell transplants for
patients less than 20 years old are cord blood transplants (mostly for ALL and AML)– Data from international Bone Marrow
Transplantation Registry
On lists around the world
• >22.5 million potential adult bone marrow donors
• >601,000 cord blood units
HLA typing
• A suitably matched adult donor is defined as one matched with the patient at ≥7/8 HLA loci (HLA-A, -B, -C, and -DRB1).
• A suitably matched CBU is defined as one matched with the patient at ≥4/6 HLA loci (HLA-A, -B, and -DRB1)
Likelihood of finding an unrelated cord blood unitRange 95-99%: patients <20 years, adequate cell dose, Be The Match Registry®
White European
Middle Eastern/N. A
frican
African Americ
anAfric
an
Black South/Centra
l Americ
an
Black Carib
bean
ChineseKorean
South Asian
JapaneseFili
pino
Southeast Asia
n
Vietnamese
Hawaiian/Pacific Is
lander
Mexican
Hispanic S
outh/Central A
merican
Hispanic C
aribbean
Native North
American
Native South/Centra
l Americ
an
Native Carib
bean
Native Alaska
n0%
10%20%30%40%50%60%70%80%90%
100%
6/6 HLA match ≥5/6 HLA match ≥4/6 HLA match
Race or ethnic group of searching patient for hematopoietic cell transplantation
Mat
ch li
kelih
ood
Gragert L, et al. N Engl J Med. 2014; 371(4): 339-348.
Likelihood of finding an unrelated cord blood unitRange 81-96%: patients ≥20 years, adequate cell dose, Be The Match Registry®
White European
Middle Eastern/N. A
frican
African Americ
anAfric
an
Black South/Centra
l Americ
an
Black Carib
bean
ChineseKorean
South Asian
JapaneseFili
pino
Southeast Asia
n
Vietnamese
Hawaiian/Pacific Is
lander
Mexican
Hispanic S
outh/Central A
merican
Hispanic C
aribbean
Native North
American
Native South/Centra
l Americ
an
Native Carib
bean
Native Alaska
n0%
10%20%30%40%50%60%70%80%90%
100%
6/6 HLA match ≥5/6 HLA match ≥4/6 HLA match
Race or ethnic group of searching patient for hematopoietic cell transplantation
Mat
ch li
kelih
ood
Gragert L, et al. N Engl J Med. 2014; 371(4): 339-348.
White
Euro
pean
Middle Ea
stern
/N. A
frica
n
Africa
n America
n
African
Black S
outh/C
entra
l Ameri
can
Black Cari
bbean
Chinese
Korean
South
Asian
Japan
ese
Filipino
South
east Asia
n
Vietnam
ese
Hawaiian
/Pac
ific Isla
nder
Mexican
Hispan
ic So
uth/C
entra
l Ameri
can
Hispan
ic Cari
bbean
Native North
America
n
Native
South
/Cen
tral A
merican
Native
Caribbea
n
Native Alas
kan
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
8/8 HLA match ≥7/8 HLA match
Race or ethnic group of searching patient for hematopoietic cell transplantation
Mat
ch li
kelih
ood
Likelihood of finding matched unrelated adult donorRange 66-97%: Available suitable match, by race/ethnic group, Be The Match Registry®
Gragert L, et al. N Engl J Med. 2014; 371(4): 339-348.
Cord blood vs Bone marrow• Advantages of cord blood
– Greater degree of HLA mismatch toleration by recipient– Decreased incidence of GVH disease
• Less CD8+ T cells in cord blood– Lower incidence of CMV and EBV transmission– Available in shorter time interval (already tested and banked)
• Around 2 weeks compared with 11-13 weeks in BM transplant– Greater proliferative and colony forming capacity
• More responsive to growth factors
• Disadvantage of cord blood– One log fewer number of stem cells acquired per unit
• Overcame by combined units of cord blood for volume expansion– Ex vivo expansion studies underway
– Slower engraftment
Limitations of autologous cord blood transplant
• Inborn errors of metabolism or other genetic diseases – Genetic mutations already present in autologous stem
cells• Somatic gene therapy research underway
• Childhood leukemia– Chromosomal translocations in fetal blood have been
detected– Negate the beneficial effect of graft vs leukemia effect in
allogenic stem cell transplants
Potential of cord tissue
• Mesenchymal stem cells– Bone– Cartilage– Myocardial muscle– Neural tissue
Biological effects of MSCs in preclinical models of disease
Research underwayNeurological• Intracranial hemorrhage• Amyotrophic lateral sclerosis• Spinal cord injury• Alzheimer's• Parkinson’s• Multiple sclerosis• Cerebral palsy
Others• Myocardial infarction• Osteoarthritis• Rheumatoid arthritis• Inflammatory bowel disease• Lung cancer
No treatment approved yet
Summary
• Non-directed donations • Directed donations for at-risk families• Personal commercial banking for low-risk
families• No alteration in usual management of the
third stage• Cord blood vs Bone Marrow• Potential of MSCs and cord tissue
Reference• Umbilical Cord Blood Banking: Scientific Advisory Committee Opinion
Paper 2, June 2006, Royal College of Obstetricians and Gynaecologists. (reaffirmed 2011)
• ACOG Committee Opinion: Umbilical cord Blood Banking, Number 399, February 2008 (Reaffirmed 2012)
• Moise KJ Jr. Umbilical cord stem cells. Obstet Gynecol 2005;106:1393-407• Antonio Uccelli, Lorenzo Moretta & Vito Pistoia Mesenchymal stem cells in
health and disease Nature Reviews Immunology 8, 726-736 (September 2008) | doi:10.1038/nri2395
• QMH OG guideline• Uptodate.com• Bethematch.org