Umbilical Cord Blood derived Stem Cells 1. Introduction Umbilical cord blood provides nourishment to the fetus and it contains a variety of stem cells that can be utilized after the baby is born. Umbilical cord blood (UCB) transplantation is used to treat both malignant and non-malignant diseases. Cord blood contains hematopoietic stem cells, mesenchymal stem cells, endothelial progenitor cells (that build new blood vessels), very small embryonic-like stem cells, unrestricted somatic stem cells, multilineage progenitor cells and neuronal progenitor cells. Cord blood is easily collected and provides a virtually unlimited supply. There are also no ethical issues with establishing public and private UCB banks throughout the world for cord blood transplantations. Matsumoto T, Mugishima H. Non-hematopoietic stem cells in umbilical cord blood. Int J Stem Cells 2009;2(2):83-9. on-line reference 2. Cord Blood and Cord Blood Banking As the popularity of human umbilical cord derived stem cells (UCBSCs) have increased in recent years, the concept of the Umbilical Cord Blood Banking for future use has also increased. Cord blood stem and progenitor cells are immature cells that, in most cases, do not cause graft vs. host reactions, even with mismatched recipients. They are also capable of producing large quantities of cells that can differentiate into neural, cardiac, epithelial, liver and skin tissues. Cord blood derived stem cells are also ethically acceptable and widely supported by the public for therapeutic use. Lee MW, Jang IK, Yoo KH, Sung KW, Koo HH. Stem and progenitor cells in human umbilical cord blood. Int J Hematol 2010; 92(1):45-51. on-line reference 3. Umbilical Cord Blood Storage Successful transplantation with stored umbilical cord stem cells transplantation depends on cell viability and graft potency. A public cord blood bank had cryopreserved sixty cord blood units for up to 8 years. The authors investigated their viability, early cell programmed death (apoptosis), and graft potency. They found that the umbilical cord blood derived hematopoietic stem cells were comparable to the fresh cord blood 48 hours after collection. There was also no acceleration of stem cell death during the storage. Kim KM, Huh JY, Hong SS, Kang MS. Assessment of cell viability, early apoptosis and hematopoietic potential in umbilical cord blood units after storage. Transfusion 2015 Apr 10 [Epub ahead of print] on-line reference B. Treatments 1. Bone Regeneration The use of postnatal cord blood mesenchymal stem cells is ethically uncomplicated (in comparison with embryonic stem cells) and requires no invasive harvesting procedure as with bone marrow and adipose tissue. Cord blood mesenchymal stem cells have good bone differentiation potential and low immunoreactivity. Jäger M1, Zilkens C, Bittersohl B, Krauspe R. Cord blood--an alternative source for bone regeneration. Stem Cell Rev 2009;5(3):266-77. on-line reference 2. Brain injury in infants and children Preterm infants who later develop cerebral palsy show evidence of white matter injury in the brain. Cord blood stem cells have shown benefits in reducing brain injury, particularly those involving hypoxia-ischemmia (lack of oxygen and blood flow). UCB stem cells are anti-inflammatory, immune-modulatory and release neuroprotective growth factors to support the brain tissue. Li J, McDonald CA, Fahey MC, Jenkin G, Miller SL. Could cord blood cell therapy reduce preterm brain injury? Front Neurol 2014;5:200. on-line reference 3. Cancer Immunotherapy Umbilical cord blood is most often used in cancer treatments for hematopoietic reconstitution. However, as awareness of the subpopulations of cord blood becomes more prominant, there will be greater utilization of this source for natural killer cells, dendritic cells and regulatory T cells against malignancies. Cany J, Dolstra H, Shah N. Umbilical cord blood-derived cellular products for cancer immunotherapy. Cytotherapy 2015 Mar 17 [Epub ahead of print] on-line reference 4. Cardiovascular Treatments Umbilical cord blood derived mesenchymal stem cells are able to differentiate into endothelial progenitor cells that can repair and produce new blood vessels and improve the vascular health of patients. Endothelial progenitor cells are being used for atherosclerosis, peripheral artery disease, and hypertension. Roura S, Pujal JM, Bayes-Genis A. Umbilical cord blood for cardiovascular cell therapy: from promise to fact. Ann NY Acad Sci 2012;1254:66-70. 92(1):45-51. on-line reference b. Heart Disease and Regenerative Medicine Transplanted stem cells work by providing trophic support to the injured tissues. They release soluble cytokines and growth factors that contribute to cardiac repair and regeneration by inducing cell protection and angiogenesis (new blood cells). Clinical trials have used cord blood for the treatment of blood malignancies as well as inborn errors of metabolism, sickle cell anemia, and autoimmune diseases. Further advances in regenerative medicine that include cardiac repair will also benefit from the use of cord blood. The cells can be delivered by an allogeneic approach (different donor and recipient), where strick tissue matching may not be necessary and where treatment is achieved by promoting trophic support rather than cell replacement. Greco N, Laughlin MJ. Umbilical cord blood stem cells for myocardial repair and regeneration. Methods Mol Biol 2010; 660:29-52. on-line reference 5. Cerebral Palsy (CP) Recent advances in regenerative medicine suggest that stem cell transplantation may provide great benefits in treating CP. The authors recommend stem cells that are safe when considering stem cells. Fan HC, Ho LI, Chi CS, Cheng SN, Juan CJ, Chiang KL, Lin SZ, Harn HJ. Current proceedings of cerebral palsy. Cell Transplant 2015;24(3):471-85. on-line reference 6. Diabetes Type 1 In 2008, the authors began a program of administering children with type 1 diabetes their own cord blood stem cells that had been saved in blood banks. The transfusions were safe and provided a slowing of the loss of the children's insulin production. Haller MJ, Viener HL, Wasserfall C, Brusko T, Atkinson MA, Schatz DA. Autologous umbilical cord blood infusion for type 1 diabetes. Exp Hematol 2008;36(6):710-5. on-line reference b. Diabetes Type 2 18 patients with type 2 diabetes were administered umbilical cord blood derived mesenchymal stem cells three times intravenously and followed for six months. Fasting plasma glucose and postprandial blood glucose levels were significantly reduced after the transfusions. All of the patients were more active and expressed a sense of well-being throughout the six month follow up. Kong D, Zhuang X, Wang D, Qu H, Jiang Y, Li X, Wu W, Xiao J, Liu X, Liu J, Li A, Wang J, Dou A, Wang Y, Sun J, Lv H, Zhang G, Zhang X, Chen S, Ni Y, Zheng C. Umbilical cord mesenchymal sem cell transfusion ameliorated hyperglycemia in patients with type 2 diabetes mellitus. Clin Lab 2014;60(12):1969-76. on-line reference 7. Liver disease BR> Mesenchymal stem cells are able to differentiate into various cell types that include hepatocytes or liver cells. Studies using mesenchymal stem cells from bone marrow or umbilical cord blood have been effective in treating patients with liver fibrosis, cirrhosis and other liver diseases. Liu WH, Song FQ, Ren LN, Guo WQ, Wang T, Feng YX, Tang LJ, Li K. The multiple functional roles of mesenchymal stem cells in participating in treating liver diseases. J Cell Mol MEd 2015;19(3):511-20. on-line reference 8. Lung Disease The authors investigated the safety and feasibility of treating preterm infants at high risk for bronchopulmonary dysplasia allogeneic (from other babies) human umbilical cord blood-derived mesenchymal stem cells. One group was given 1 million stem cells per kilogram (low dose) and another group was given 2 million stem cells per kilogram (high dose) and compared with a control group. The therapies were well tolerated and by day 7 had significantly reduced inflammatory cytokines in the trachea. The treatment group had improved to a greater extent than those in the control group. The authors conclude that the stem cell treatment is safe and feasible and should be extended to a larger treatment group. Chang YS, Ahn SY, Yoo HS, Sung SI, Choi SJ, Oh WI, Park WS. Mesenchymal stem cells for bronchopulmonary dysplasia: phase 1 dose-escalation clinical trial. J Pediatr 2014;164(5):966-972.e6. on-line reference 9. Lysosomal storage diseases Umbilical cord blood is now considered to be the optimal source of hematopoietic stem cells for treating lysosomal storage disorders. The transplantation extends survival by providing a continuous supply of enzymes through the cord cells. Aldenhoven M, Kurtzberg J. Cord blood is the optimal graft source for the treatment of pediatric patients with lysosomal storage diseases: clinical outcomes and future directions. Cytotherapy 2015;17(6):765-74. on-line reference 10. Sickle Cell Disease Allogeneic (different donor and recipient) hematopoietic stem cell transplantation has proven beneficial in controlling sickle cell disease related vascular pathology and organ damage. Umbilical cord blood contains hematopoietic stem cells and can also provide benefits for sickle cell disease. Shenoy S. Umbilical cord blood: an evolving stem cell source for sickle cell disease transplants. Stem Cells Transl Med 2013; 2(5):337-40. on-line reference