Transplanting Stem Cells from Umbilical Cord Blood - Overview
Studies on umbilical cord blood began in the 1960s, leading to successful transplants for various conditions. Cord blood, rich in hematopoietic stem cells, can be stored for future use. The transplant process involves pre-treatment, obtaining cord blood, intravenous transfusion, and new blood cell production in the patient. The first cord blood transplant in 1988 treated Fanconi's Anemia successfully. Cord blood banking is an option for parents to consider for potential future medical needs.
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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
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
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 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
Blood 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 (RAEB- T) Refractory Anemia with Ringed Sideroblasts (RARS) Shwachman-Diamond Syndrome Sickle Cell Disease Metabolic Disorders 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, 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)
PROS AND CONS OF BLOOD BANKING https://www.youtube.com/watch?v=Bnz RzKsvlDo&index=44&list=PLturoXTpuYxD ZkWOka_1SJ1icT-fxZqfP
Disadvantages Benefits 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 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)
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 Changes DUTY TO FEEDBACK CHANGES IN LAW FOR THE COMMERCIAL SECTOR A donor should have the right to know if the researcher has come across a potential risk for their health within the study. 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.
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- Sch nberg 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 Quinns 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) Na ve 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 patients 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- 20019296 anemia/basics/causes/con- 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- March 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., K gler, G., Bruckner, B., & ... Ruhparwar, A. (2011). Transplanted human cord blood-derived unrestricted somatic stem cells preserve high-energy reserves at the site of acute 13(8), 956-961. doi:10.3109/14653249.2011.563290 myocardial infarction. Cytotherapy (Taylor & Francis Ltd), 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 Fanconi's Anemia by Means of Umbilical-Cord Blood from an HLA-Identical Sibling. Ilic, D. (2014). The Legal Duties of Stem Cell Banks with Regard to Stem Cell Donors and Recipients. In Stem Cell Banking (pp. 41- Springer. Reconstitution in a Patient with NewEngland Journal of Medicine, 1174-1178. 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 Medicine, 11(1), 1-10. doi:10.1186/1479-5876-11-196
