Shilpa Sharma, Gurudutta Gangenahalli (2015) Umbilical Cord Blood Transplantation: Clinical Challenges. Int J Stem Cell Res Transplant, 03(6), 134-141. 134 http://scidoc.org/IJST.php Umbilical Cord Blood Transplantation: Clinical Challenges Review Article Shilpa Sharma & Gurudutta Gangenahalli * Division of Stem Cell Gene Therapy Research, Institute of Nuclear Medicine & Allied Sciences (INMAS), Delhi-110054, India. *Corresponding Author: Dr. Gurudutta Gangenahalli PhD, FRSC (UK)., Head, Division of Stem Cell Gene Therapy Research, In- stitute of Nuclear Medicine & Allied Sciences (INMAS), Delhi-110054, India. Tel: 91-11-23905144 Fax: 91-11-25737049 Email: gugdutta@rediffmail.com Received: October 09, 2015 Accepted: December 07, 2015 Published: December 10, 2015 Citation: Shilpa Sharma, Gurudutta Gangenahalli (2015) Umbilical Cord Blood Transplantation: Clinical Challenges. Int J Stem Cell Res Transplant 03(6), 134-141. Copyright: Gurudutta Gangenahalli © 2015. This is an open-access ar- ticle distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited. Introduction Hematopoietic stem cells (HSCs) are the prototype stem cells en- dowed with the potential of restoring hematopoiesis in patients with hematological malignancies. Clinical transplantation results are best obtained by HLA identical donor or closely related donor. In spite of nearly 13 million registered volunteer donors world- wide, nearly half of the patients do not have a closely matched HLA donor and two-thirds of patients do not get suitable related donor. In such a situation, availability of unrelated donor (URD) from bone marrow (BM), peripheral blood stem cells (PBSC) and umbilical cord blood (UCB) escalate the applicability of HSCT. Though BM and PBSC transplantation have proven record of success, only 40-50% of unrelated BM and PBSC donor setting provide prompt graft source for patients [1]. In the early 1980s, Broxmeyer et al introduced UCB as a potential source of HSCs and progenitor cells which provided impetus to perform the irst UCB transplant for a patient with fanconi anemia in 1988 [2, 3]. The paucity of HSCs in UCB grafts has been a major limitation of UCB transplantation. UCB grafts have been shown to contain ten-fold lower cellular dose (nucleated and CD34 + cells) com- pared to BM and PB transplantation, which has translated into delayed engraftment and immune reconstitution [4]. However, there is a recent report that demonstrates that there are actually more HSCs in UCB than previously realized [5]. A brief exposure to ambient oxygen in native conditions of hypoxia reportedly de- creases recovery of long-term repopulating HSCs and increases progenitor cells in UCB. HSC collection in grossly hyperoxic con- ditions compared to the BM microenvironment [6] compromises the survival of HSCs through the induction of the mitochondrial permeability transition pore (MPTP) and ROS production. The MPTP inhibitor cyclosporin. A protects HSCs during collection in air, allowing collection of more number of HSCs in UCB for potential clinical beneit [5]. In unrelated UCB banks, UCB units are rapidly available as “off the shelf ” product for narrowing the gap of a growing popu- lation of patients who do not have an identiied HLA matched relative. Moreover, use of a frozen graft allows scheduling of stem cell collections and date of transplant without losing repop- ulation capacity on post-thawing [7]. Frozen UCB units can be stored for long duration and then thawed for eficient recovery of HSCs and progenitor cells in relevance to UCB banking and transplantation, Broxmeyer et al. evaluated recovery of function- ally-intact hematopoietic progenitor cells for up to 23.5 years in comparison to pre-freeze numbers from the same donor. Highly International Journal of Stem Cell Research and Transplantation (IJST) ISSN 2328-3548 Abstract Umbilical cord blood transplantation (UCBT) is becoming a salvage treatment in lieu of bone marrow or peripheral blood stem cell transplantation in patients with hematological disorders who lack human leucocyte antigen (HLA) identical stem cell donor. Additionally, this procedure has demonstrated reduced recurrent acute and chronic graft-versus-host disease, reduced relapse rates, long-term immunological recovery and comparable overall survival when compared with other un- related allogeneic hematopoietic stem cell transplantation. UCBT is further elucidated by its easy procurement, expeditious availability and more tolerance for HLA mismatches. Discerningly, UCBT is followed by notable delays in the rates and kinetics of neutrophil and platelet engraftment and higher transplant related mortality. This is related in part to the inher- ently lessened number of hematopoietic stem and progenitor cells in UCB grafts. Several strategies have been assayed to overcome relatively limited number of stem cells, such as multiple UCB transplants and ex vivo expansion of HSCs. In this review, we have compiled the current clinical research investigations to provide reader with a brief glimpse into the remark- able potential UCB possess for transplantation. Keywords: Hematopoietic Stem and Progenitor Cells; Umbilical Cord Blood Transplantation; ex vivo Expansion; Engraftment.