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 theTransplanting 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 DisordersAdenosine Deaminase Deficiency (SCID)Bare Lymphocyte Syndrome (SCID)Chediak-Higashi Syndrome (SCID)Chronic Granulomatous DiseaseCongenital NeutropeniaDiGeorge SyndromeEvans SyndromeFucosidosisHemophagocytic Lymphohistiocytosis (HLH)Hemophagocytosis Langerhans’ Cell Histiocytosis (Histiocytosis X)IKK Gamma Deficiency (NEMO Deficiency)Immune Dysregulation, olyendocrinopathy, Enteropathy, X-linked (IPEX) SyndromeKostmann Syndrome (SCID)MyelokathexisOmenn Syndrome (SCID)Phosphorylase Deficiency (SCID)Purine Nucleoside (SCID)Reticular Dysgenesis (SCID)Severe Combined Immunodeficiency Diseases (SCID)Thymic DysplasiaWiskott-Aldrich SyndromeX-linked AgammaglobulinemiaX-Linked Lymphoproliferative DisorderX-Linked Hyper IgM Syndrome

CancersAcute Biphenotypic LeukemiaAcute Lymphocytic Leukemia (ALL)Acute Myelogenous Leukemia (AML)Acute Undifferentiated LeukemiaAdult T Cell Leukemia/LymphomaChronic Active Epstein BarrChronic Lymphocytic Leukemia (CLL)Chronic Myelogenous Leukemia (CML)Ewing SarcomaHodgkin’s LymphomaJuvenile Chronic Myelogenous Leukemia (JCML)Juvenile Myelomonocytic Leukemia (JMML)Myeloid/Natural Killer (NK) Cell PrecursorAcute LeukemiaNon-Hodgkin’s LymphomaProlymphocytic LeukemiaPlasma Cell LeukemiaChronic Myelomonocytic Leukemia (CMML)Leukocyte Adhesion DeficiencyMultiple MyelomaNeuroblastomaRhabdomyosarcomaThymoma (Thymic Carcinoma)Waldenstrom’s MacroglobulinemiaWilms Tumor

Blood DisordersAcute MyelofibrosisAgnogenic Myeloid Metaplasia (Myelofibrosis)AmyloidosisAplastic Anemia (Severe)Beta Thalassemia MajorBlackfan-Diamond AnemiaCongenital Amegakaryocytic Thrombocytopenia (CAT)Congenital CytopeniaCongenital Dyserythropoietic AnemiaDyskeratosis CongenitaEssential ThrombocythemiaFanconi AnemiaGlanzmann’s ThrombastheniaMyelodysplastic SyndromeParoxysmal Nocturnal Hemoglobinuria (PNH)Polycythemia VeraPure Red Cell AplasiaRefractory Anemia with Excess Blasts (RAEB)Refractory Anemia with Excess Blasts in Transition (RAEB-T)Refractory Anemia with Ringed Sideroblasts (RARS)Shwachman-Diamond SyndromeSickle Cell Disease

Metabolic DisordersCongenital Erythropoietic Porphyria (Gunther Disease)Gaucher DiseaseHunter Syndrome (MPS-II)Hurler Syndrome (MPS-IH)Krabbe DiseaseLesch-Nyhan SyndromeMannosidosisMaroteaux-Lamy Syndrome (MPS-VI)Metachromatic LeukodystrophyMucolipidosis II (I-cell Disease)Neuronal Ceroid Lipofuscinosis (Batten Disease)Niemann-Pick DiseaseSandhoff DiseaseSanfilippo Syndrome (MPS-III)Scheie Syndrome (MPS-IS)Sly Syndrome (MPS-VII)Tay SachsWolman DiseaseX-Linked Adrenoleukodystrophy

USE IN AUTISM• Unlike other medications that focus to control the behavior, targets the

observed molecular mechanisms. • Abnormal neurotransmitter regulation, mitochondrial dysfunction, blood-

brain 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 self-attack

• 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=BnzRzKsvlDo&index=44&list=PLturoXTpuYxDZkWOka_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. Cost-Effectiveness 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 ChangesCHANGES 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 Albers-

Schönberg 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/aplastic- anemia/basics/causes/con-20019296

Apurva. (2009, January 11). Advantages and Disadvantages of Cord Blood Treatment. Retrieved from http://www.disabled-world.com/news/research/stemcells/cordblood-treatment.php

Brown, N., & Kraft, A. (2007). Blood Ties: Banking the Stem Cell Promise. Technology Analysis & Strategic Management, 313- 327. Retrieved March 14, 2015, from Taylor & Francis Online

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 cell treatments for cerebral palsy in Australia. Journal Of Paediatrics & Child Health, 50(7), 540-544. doi:10.1111/jpc.12618

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. Transfusion, 2010-2010.

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. 41- 49). Dordrecht: Springer.

References (cont.)

Kiatpongsan, S. (2008). Business on Hope: A Case Study on Private Cord Blood Stem Cell Banking. Chot Mai Het Thang Phaet, 91(4), 577-580. Retrieved March 1, 2015, from PubMed.gov.

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_Cord_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=CjwKEAjw25SoBRCMn7Gc97Knj0ISJAC7vaMrN8iRvSNFzlTCH96F_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

Medicine, 11(1), 1-10. doi:10.1186/1479-5876-11-196