Transcript Transplanting Stem Cells From Umbilical Cord Blood

Transplanting Stem Cells From
Umbilical Cord Blood
CAROLINE CAVANAUGH, NISHA LIPOWCAN, VALERIE KATULKA, WILL WATSON,
EMILY BRATLEE, SHAYNA SVARANOWIC, MAGGIE MCCALL
Prior to this class, did you know that
pulling stem cells from the umbilical
cord was possible?
A. Yes
B. No
Based off the title of our presentation,
Transplanting Stem Cells from Umbilical Cord
Blood, would you bank your child’s cord blood?
A. Yes
B. No
Background and the
Transplanting Process
Umbilical Cord Blood
• Studies of umbilical cord blood began in the 1960s
• About 1 in 3 hematopoietic stem cell transplants are
done with cord blood
• The blood that is left in the placenta and umbilical cord
can be taken and stored to be used for a stem cell
transplant later in life
https://www.youtube.com/watch?v=WGAcVLm9pBI
Transplant Process
• Pre-Transplant
• Patients receive other forms of treatment
• Cord Blood is obtained
• Transplant
• Patient receives the cord blood intravenously
• Post-Transplant
• Stem cells travel to the patient’s bone marrow
• Stem cells produce new WBC, RBC and platelets
First Cord Blood Transplant
• In 1988, a pediatric patient with Fanconi’s Anemia was successfully
treated with a transplant of hematopoietic stem cells (HSC) from
umbilical cord blood (UCB)
• Fanconi’s Anemia: develops because of damage done to the bone marrow
which is causing the bone marrow to slow or stop new blood cell production
• The Ende brothers are accredited with clinical observation,
establishing the scientific basis of the observation and performing the
first transplant
• Dr. Broxmeyer is accredited for his studies on the storage of the UCB
• Dr. Gluckman is accredited for her efforts that established the
transplantation of HSC from UCB as an accepted therapy
Uses For Cord Blood
• Treatment for over 80 diseases
• 1988 – 1 disease
• 2007 – 40 diseases
• 2010 – 80 diseases
• Not a cure but regenerates damaged tissues and restores lost function
after injury or illness.
• Also used to regenerate healthy blood and immune systems after
being damaged by diseases.
• Mostly used in children and small adults because not enough blood
can be acquired from umbilical cord that is needed for the adult
Immune Disorders
Adenosine Deaminase Deficiency (SCID)
Bare Lymphocyte Syndrome (SCID)
Chediak-Higashi Syndrome (SCID)
Chronic Granulomatous Disease
Congenital Neutropenia
DiGeorge Syndrome
Evans Syndrome
Fucosidosis
Hemophagocytic Lymphohistiocytosis (HLH)
Hemophagocytosis Langerhans’ Cell Histiocytosis
(Histiocytosis X)
IKK Gamma Deficiency (NEMO Deficiency)
Immune Dysregulation,
olyendocrinopathy, Enteropathy, X-linked (IPEX)
Syndrome
Kostmann Syndrome (SCID)
Myelokathexis
Omenn Syndrome (SCID)
Phosphorylase Deficiency (SCID)
Purine Nucleoside (SCID)
Reticular Dysgenesis (SCID)
Severe Combined Immunodeficiency Diseases (SCID)
Thymic Dysplasia
Wiskott-Aldrich Syndrome
X-linked Agammaglobulinemia
X-Linked Lymphoproliferative Disorder
X-Linked Hyper IgM Syndrome
Cancers
Acute Biphenotypic Leukemia
Acute Lymphocytic Leukemia (ALL)
Acute Myelogenous Leukemia (AML)
Acute Undifferentiated Leukemia
Adult T Cell Leukemia/Lymphoma
Chronic Active Epstein Barr
Chronic Lymphocytic Leukemia (CLL)
Chronic Myelogenous Leukemia (CML)
Ewing Sarcoma
Hodgkin’s Lymphoma
Juvenile Chronic Myelogenous Leukemia (JCML)
Juvenile Myelomonocytic Leukemia (JMML)
Myeloid/Natural Killer (NK) Cell PrecursorAcute
Leukemia
Non-Hodgkin’s Lymphoma
Prolymphocytic Leukemia
Plasma Cell Leukemia
Chronic Myelomonocytic Leukemia (CMML)
Leukocyte Adhesion Deficiency
Multiple Myeloma
Neuroblastoma
Rhabdomyosarcoma
Thymoma (Thymic Carcinoma)
Waldenstrom’s Macroglobulinemia
Wilms Tumor
Blood Disorders
Metabolic Disorders
Acute Myelofibrosis
Agnogenic Myeloid Metaplasia (Myelofibrosis)
Amyloidosis
Aplastic Anemia (Severe)
Beta Thalassemia Major
Blackfan-Diamond Anemia
Congenital Amegakaryocytic Thrombocytopenia (CAT)
Congenital Cytopenia
Congenital Dyserythropoietic Anemia
Dyskeratosis Congenita
Essential Thrombocythemia
Fanconi Anemia
Glanzmann’s Thrombasthenia
Myelodysplastic Syndrome
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Polycythemia Vera
Pure Red Cell Aplasia
Refractory Anemia with Excess Blasts (RAEB)
Refractory Anemia with Excess Blasts in Transition (RAEBT)
Refractory Anemia with Ringed Sideroblasts (RARS)
Shwachman-Diamond Syndrome
Sickle Cell Disease
Congenital Erythropoietic Porphyria (Gunther Disease)
Gaucher Disease
Hunter Syndrome (MPS-II)
Hurler Syndrome (MPS-IH)
Krabbe Disease
Lesch-Nyhan Syndrome
Mannosidosis
Maroteaux-Lamy Syndrome (MPS-VI)
Metachromatic Leukodystrophy
Mucolipidosis II (I-cell Disease)
Neuronal Ceroid Lipofuscinosis (Batten Disease)
Niemann-Pick Disease
Sandhoff Disease
Sanfilippo Syndrome (MPS-III)
Scheie Syndrome (MPS-IS)
Sly Syndrome (MPS-VII)
Tay Sachs
Wolman Disease
X-Linked Adrenoleukodystrophy
USE IN AUTISM
•
Unlike other medications that focus to control the behavior, targets the
observed molecular mechanisms.
• Abnormal neurotransmitter regulation, mitochondrial dysfunction, bloodbrain barrier disruptions
•
Study
• Combined transplantation of human cord blood mononuclear cells
(CBMNCs) and umbilical cord derived mesenchymal stem cells (UCMSCs)
•
•
Improved behavior and function
Safe to use
USE IN CEREBRAL PALSY
•
Umbilical cord blood shown to lessen the impact of injury and
facilitate neural cell repair resulting in improved function for
patients with cerebral palsy
•
Study
• Peripheral mononuclear blood stem cells used
• Resulted in functional improvements
• Safe to use
USE IN HEART FAILURE
•
CB stem cells are capable of giving rise to hematopoietic,
epithelial, endothelial and neural tissues
•
Study
•
•
•
Cord blood-derived unrestricted somatic stem cells (USSC) used
in patients with acute ischemic myocardium
Mesenchymal stem cells
Functional improvements observed but not full recovery
USE IN STROKE
•
Help in stroke recovery and brain repair by angiogenesis and
neurogenesis with restoration to cortical tissue
•
Study
• CD34+ of umbilical cord blood
• Successful outcomes in animal testing
USE IN OSTEOARTHRITIS
•
Allogenic mesenchymal stem cells from donated human umbilical
cords are administered into the affected joint(s) (intra-articular
injection) and intravenously
•
Vet-Stem tested and uses stem cells on horses with various joint
deformities to accelerate healing
•
Stem cells can protect cartilage from further destruction and facilitate
regeneration
•
Typical treatment protocol at Stem Cell Institute is about 5 days
(Riordan, 2012)
USE IN RHEUMATOID ARTHRITIS
Other treatments have long-term adverse effects and do not
address the issue of damage that has already occurred
• Mesenchymal stem cells produce anti-inflammatory agents,
which act locally and do not suppress the immune response of
the patient’s whole body
• Induce the production of T regulatory cells, a type of immune cell
whose function is to protect the body against immunological selfattack
• Typical treatment protocol is 4 days
•
(Riordan, 2012)
USE IN SPINAL CORD INJURY
•
Typical treatment protocol calls for 16 intravenous and intrathecal injections over the
course of 4 weeks and uses a combination of umbilical cord derived stem cells and
bone-marrow derived stem cells
•
Intrathecal injections enable the stem cells to bypass the blood-brain barrier and
migrate to the injury site
•
Study
• Treatment was effective in 13 out of 22 patients (81.25% effective in incomplete
SCI, not effective in any patients with complete SCI)
• Patients reported significantly improved tactile sensation, motion and activities of
daily living
•
Real-life Success Story: Jamie Richie
(Riordan, 2012)
Ethical Issues
PROS AND CONS OF BLOOD BANKING
https://www.youtube.com/watch?v=Bnz
RzKsvlDo&index=44&list=PLturoXTpuYxD
ZkWOka_1SJ1icT-fxZqfP
Benefits
•
Proven to treat
hematopoietic diseases
•
One umbilical cord
generally contains enough
stem cells to treat a child
or small adult
•
Previously, treating with
two different donors has
been effective which is
reassuring in showing how
adaptable cord blood cells
are
(Apurva, 2009)
Disadvantages
• Expensive
• Chance that patient is
exposed to a rare genetic
disorder of the immune
system or blood
• It may take a decade or two
before there is a definite
cure to deadly diseases
• The average-sized or larger
adults were not thought to be
able to benefit from this type
of treatment
Ethical Areas to Think About
•
Respect for human dignity and integrity
•
Autonomy
•
Justice and Solidarity
•
Beneficence
•
Non-maleficence
•
Proportionality
(Petrini, 2013)
Cord Blood: Ethics
•
Justice
Sufficient donations from different ethic groups
• Public storage when possible
•
(Petrini, 2013)
Cord Blood: Ethics
•
Public or Private cord banking
•
Public: Even discarded blood can benefit
•
Private: The use for self is rare (0.005%)
(Petrini, 2013)
Fig. 3. Monte Carlo
simulation; 7,500 trials
performed. Points that lie
below the dotted line
represent trials in which
private cord blood
banking was cost-effective
at a threshold of
$100,000.Kaimal. CostEffectiveness of Cord
Blood Banking. Obstet
Gynecol 2009.
Cord Blood: Ethics
•
Informed Consent
•
Autonomy: right to self-determination
•
USA: Laws aimed at educating parents about CB
•
Process of obtaining informed consent should begin BEFORE labor and
delivery
(Petrini, 2013)
Business On Hope
•
New model of business that sells only “the hope on future
use.”
•
High use of Propaganda or Persuasion by private blood bank
company’s on potential clients.
Misinformed Mothers
•
Claim 1: Your child will most likely need their stored blood, the one company
claims 1 in every 50 children.
•
Claim 2: The child can use their own cord blood to treat leukemia.
•
Claim 3: Stem cells in cord blood can be used as a cure-all for adults in
treating many diseases.
•
Claim 4: Finding a stem cell donor is often impossible.
•
The Society of Obstetricians and Gynecologists and The American Academy
of Pediatrics does not recommend cord blood banking.
(Marketplace: Busted: Cord Blood Banks)
Proposed Changes
CHANGES IN LAW FOR THE
COMMERCIAL SECTOR
•
Allow donors to have the right
to know what exactly their
donations will be used for and
how they are being used.
•
Allow donors to obtain profits
from products or tests
developed from their samples.
“DUTY TO FEEDBACK”
•
A donor should have the right
to know if the researcher has
come across a potential risk for
their health within the study.
Cord Blood Cell Stories
The Dones’ Story
•
Tracey and Victor’s son Anthony diagnosed with Osteopetrosis
at 4 months old
•
Osteopetrosis, "stone bone", also known as marble bone disease and AlbersSchönberg disease, is an extremely rare inherited disorder whereby the bones
harden, becoming denser
•
Chose to save and store Anthony’s cord blood at birth
•
Why were they unable to use the stem cell’s from the cord blood
…?
• Stem cells contained the same genetic defect
that caused his condition
"The materials provided by the bank said this was Anthony's life insurance and could
save him if he needed it. They never mentioned that the cells could be diseased.”
Jessie Quinn’s Story
•
Mixed race woman Diagnosed with Acute Myelogenous Leukemia as an
adult and was selected to participate in a study done by the SCCA
working with cord blood transplants in Adults
•
The nature of cord cells is unique (cells haven’t been educated against
foreign invaders like bacteria and viruses)
•
Naïve immune system of cord blood means that close HLA tissue-type
DNA matching is much less important for cord blood than it is for bone
marrow transplants
•
It takes more time to restore a patient’s blood counts after cord
blood transplantation than with bone marrow or adult blood cells.
This makes cord blood transplant patients more vulnerable to
infections early.
•
Doctor’s used a public cord blood bank with 2 units of primary cord
blood and one unit of “expanded” cord blood (to overcome the
delay in WBC production/decrease the risk of Jessie acquiring an
infection soon after transplantation)
•
Expanded cord blood cells are frozen and made readily available for patients
After hearing our presentation, would you bank
your child’s cord blood?
A. Yes
B. No
If you answered yes, would you choose
private or public banking?
A. Private
B. Public
References
ABC News. (2010, May 6). Questions about cord blood banking. Retrieved from
https://www.youtube.com/watch?v=BnzRzKsvlDo&index=44&list=PLturoXTpuYxDZkWOka_1SJ1icT-fxZqfP
Aplastic anemia. (n.d.). Retrieved March 10, 2015, from http://www.mayoclinic.org/ diseases- conditions/aplastic20019296
anemia/basics/causes/con-
Apurva. (2009, January 11). Advantages and Disadvantages of Cord Blood Treatment. Retrieved from http://www.disabledworld.com/news/research/stemcells/cordblood-treatment.php
Brown, N., & Kraft, A. (2007). Blood Ties: Banking the Stem Cell Promise. Technology Analysis & Strategic Management, 313March 14, 2015, from Taylor & Francis Online
327. Retrieved
Cord Blood Transplants. (n.d.). Retrieved March 10, 2015.
Crompton, K. E., Elwood, N., Kirkland, M., Clark, P., Novak, I., & Reddihough, D. (2014). Feasibility of trialling cord blood stem
cerebral palsy in Australia. Journal Of Paediatrics & Child Health, 50(7), 540-544. doi:10.1111/jpc.12618
cell treatments for
Ghodsizad, A., Ungerer, M. N., Bordel, V., Kallenbach, K., Kögler, G., Bruckner, B., & ... Ruhparwar, A. (2011). Transplanted human cord blood-derived
unrestricted somatic stem cells preserve high-energy reserves at the site of acute
myocardial infarction. Cytotherapy (Taylor & Francis Ltd),
13(8), 956-961. doi:10.3109/14653249.2011.563290
Glasser, L. (n.d.). The Ende brothers and the arcane history of the first umbilical cord blood hematopoietic stem cell transplant.
2010.
Transfusion, 2010-
Gluckman, E., Broxmeyer, H., Auerbach, A., Friedman, H., Douglas, G., Devergie, A., Boyse, E. (1989). Hematopoietic
Reconstitution in a Patient with
Fanconi's Anemia by Means of Umbilical-Cord Blood from an HLA-Identical Sibling.
New England Journal of Medicine, 1174-1178.
Ilic, D. (2014). The Legal Duties of Stem Cell Banks with Regard to Stem Cell Donors and Recipients. In Stem Cell Banking (pp. 41Springer.
49). Dordrecht:
References (cont.)
Kiatpongsan, S. (2008). Business on Hope: A Case Study on Private Cord Blood Stem Cell Banking. Chot Mai Het
91(4), 577-580. Retrieved March 1, 2015, from PubMed.gov.
Thang Phaet,
Kaimal, A., Smith, C., Laros, R., Caughey, A., & Cheng, Y. (2009). Cost-effectiveness Of Private Umbilical Cord Blood Banking.
Obstetrics & Gynecology, 114(4), 848-855. Retrieved March 12, 2015, from
http://journals.lww.com/greenjournal/Fulltext/2009/10000/Cost_effectiveness_ofPrivate_Umbilical_C
ord_Blood.21.aspx?WT.mc_id=EmxALLx20100222xxFRIEND#P27
Marketplace: Busted: Cord Blood Banks. Retrieved from https://www.youtube.com/watch?v=f0qr8Xpoa2Q
Moninger, J. (2014) The cord blood controversy.
Peterson, D. A. (2004). Umbilical cord blood cells and brain stroke injury: bringing in fresh blood to address an old problem. Journal
of Clinical Investigation, 114(3), 312–314. doi:10.1172/JCI200422540
Petrini, C. (2013). Ethical issues in umbilical cord blood banking: a comparative analysis of documents from national and
international institutions. Transfusion, 53(4), 902-910. doi:10.1111/j.1537- 2995.2012.03824.x
Riordan, N. (2012). Stem cell institute. Retrieved from http://www.the-stem cellinstitute.com/?gclid=CjwKEAj
w25SoBRCMn7Gc97Knj0ISJAC7vaMrN8iRvSNFzlTCH96F_jRS_2ABrlb4Hdg3d4xtLJzVBoCZZ3w_wcB
Seattle Cancer Care Alliance – Jessie Quinn
Stem Cell Transplants (Peripheral Blood, Bone Marrow, and Cord Blood Transplants). (2013, October 2). Retrieved March 10, 2015.
Yong-Tao, L., Yun, Z., Min, L., Jia-na-ti, Q., Ashwood, P., Sungho Charles, C., & ... Xiang, H. (2013). Transplantation of human cord
blood mononuclear cells and umbilical cord-derived mesenchymal stem cells in autism. Journal Of Translational
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