Fetal and Neonatal Stem Cells Concise Review : Umbilical Cord Blood Transplantation : Past , Present , and Future

Allogeneic hematopoietic stem cell transplantation is an important treatment option for fit patients with poor-risk hematological malignancies; nevertheless, the lack of available fully matched donors limits the extent of its use. Umbilical cord blood has emerged as an effective alternate source of hematopoietic stem cell support. Transplantation with cord blood allows for faster availability of frozen sample and avoids invasive procedures for donors. In addition, this procedure has demonstrated reduced relapse rates and similar overall survival when compared with unrelated allogeneic hematopoietic stem cell transplantation. The limited dose of CD34-positive stem cells available with single-unit cord transplantation has been addressed by the development of double-unit cord transplantation. In combination with improved conditioning regimens, double-unit cord transplantation has allowed for the treatment of larger children, as well as adult patients with hematological malignancies. Current excitement in the field revolves around the development of safer techniques to improve homing, engraftment, and immune reconstitution after cord blood transplantation. Here the authors review the past, present, and future of cord transplantation. STEM CELLS TRANSLATIONAL MEDICINE 2014;3:1435–1443

[1]  S. Forman,et al.  Hematopoietic Cell Transplantation , 2015 .

[2]  C. Schaniel,et al.  Epigenetic reprogramming induces the expansion of cord blood stem cells. , 2014, The Journal of clinical investigation.

[3]  M. Laughlin,et al.  Outcomes of Double Unit Umbilical Cord Blood Transplantation Using Fludarabine/Busulfan Based Reduced Intensity Conditioning Regimen , 2014 .

[4]  E. Shpall,et al.  Characteristics and Outcome of Cytomegalovirus (CMV) Infections in 95 Cord Blood Transplant (CBT) Recipients: The MD Anderson Experience , 2014 .

[5]  J. Goldberg,et al.  High Disease-Free Survival and Enhanced Protection Against Relapse after Double-Unit Cord Blood Transplantation (DCB-T) When Compared to Unrelated Donor Transplantation (URD-T) in Patients with Acute Leukemia, MDS and CML , 2014 .

[6]  W. Hwang,et al.  Double Unit Umbilical Cord Blood Transplant for Adults with Acute Leukemia and Myelodysplastic Syndrome Results in Comparable Outcome As Matched Sibling or Unrelated Donor Transplant Only after Myeloablative Conditioning but Not Reduced Intensity Conditio , 2014 .

[7]  K. Rezvani,et al.  Fucosylation with fucosyltransferase VI or fucosyltransferase VII improves cord blood engraftment. , 2014, Cytotherapy.

[8]  L. Zon,et al.  Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation. , 2013, Blood.

[9]  Elizabeth J. Shpall,et al.  Antigen Presenting Cell-Mediated Expansion of Human Umbilical Cord Blood Yields Log-Scale Expansion of Natural Killer Cells with Anti-Myeloma Activity , 2013, PloS one.

[10]  K. Ahn,et al.  Long-term survival after alternative donor transplantation in children with acute leukemia. , 2013 .

[11]  A. Fischer,et al.  Outcomes of transplantation using various hematopoietic cell sources in children with Hurler syndrome after myeloablative conditioning. , 2013, Blood.

[12]  R. Larson,et al.  Immune reconstitution after combined haploidentical and umbilical cord blood transplant , 2013, Leukemia & lymphoma.

[13]  J. Kurtzberg,et al.  Impact of Selection of Cord Blood Units from the United States and Swiss Registries on the Cost of Banking Operations , 2013, Transfusion Medicine and Hemotherapy.

[14]  E. Shpall,et al.  Cord blood graft engineering. , 2013, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[15]  Mark Munsell,et al.  Cord-blood engraftment with ex vivo mesenchymal-cell coculture. , 2012, The New England journal of medicine.

[16]  S. Spellman,et al.  Unrelated donor cord blood transplantation for children with severe sickle cell disease: results of one cohort from the phase II study from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). , 2012, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[17]  E. Shpall,et al.  Ex vivo fucosylation improves human cord blood engraftment in NOD-SCID IL-2Rγ(null) mice. , 2012, Experimental hematology.

[18]  A. Fischer,et al.  Transplantation in patients with SCID: mismatched related stem cells or unrelated cord blood? , 2012, Blood.

[19]  J. Wagner,et al.  Factors Predicting Single-Unit Predominance after Double Umbilical Cord Blood Transplantation , 2011, Bone Marrow Transplantation.

[20]  J. Wagner,et al.  Reduced-intensity conditioning transplantation in acute leukemia: the effect of source of unrelated donor stem cells on outcomes. , 2010, Blood.

[21]  E. Gluckman,et al.  Milestones in umbilical cord blood transplantation , 2011, British journal of haematology.

[22]  J. Wingard,et al.  Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts. , 2011, Blood.

[23]  B. Cooper The Origins of Bone Marrow as the Seedbed of Our Blood: From Antiquity to the Time of Osler , 2011, Proceedings.

[24]  J. Wagner,et al.  Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. , 2011, Blood.

[25]  Colleen Delaney,et al.  Allogeneic hematopoietic cell transplantation for hematologic malignancy: relative risks and benefits of double umbilical cord blood. , 2010, Blood.

[26]  S. Parmar,et al.  Umbilical cord blood transplantation. , 2010, Clinical advances in hematology & oncology : H&O.

[27]  J. Wagner,et al.  Effect of graft source on unrelated donor haemopoietic stem-cell transplantation in adults with acute leukaemia: a retrospective analysis. , 2010, The Lancet. Oncology.

[28]  E. Gluckman,et al.  Double cord blood transplantation: extending the use of unrelated umbilical cord blood cells for patients with hematological diseases. , 2010, Best practice & research. Clinical haematology.

[29]  Colleen Delaney,et al.  Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution , 2010, Nature Medicine.

[30]  I. Bernstein,et al.  Single-unit dominance after double-unit umbilical cord blood transplantation coincides with a specific CD8+ T-cell response against the nonengrafted unit. , 2010, Blood.

[31]  E. Shpall,et al.  Ex vivo expansion of cord blood , 2009, Bone Marrow Transplantation.

[32]  P. Hanley,et al.  Functionally active virus-specific T cells that target CMV, adenovirus, and EBV can be expanded from naive T-cell populations in cord blood and will target a range of viral epitopes. , 2009, Blood.

[33]  I. Millán,et al.  Cord blood transplants supported by co-infusion of mobilized hematopoietic stem cells from a third-party donor , 2009, Bone Marrow Transplantation.

[34]  J. Wagner,et al.  Analysis of risk factors for outcomes after unrelated cord blood transplantation in adults with lymphoid malignancies: a study by the Eurocord-Netcord and lymphoma working party of the European group for blood and marrow transplantation. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[35]  J. Sampath,et al.  Prostaglandin E 2 enhances hematopoietic stem cell homing , survival , and proliferation , 2009 .

[36]  J. Wagner,et al.  Umbilical cord blood transplantation. , 2009, Cancer treatment and research.

[37]  M. Gobbi,et al.  Direct intrabone transplant of unrelated cord-blood cells in acute leukaemia: a phase I/II study. , 2008, The Lancet. Oncology.

[38]  K. Ballen,et al.  The national marrow donor program 20 years of unrelated donor hematopoietic cell transplantation. , 2008, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[39]  A. Nagler,et al.  Transplantation of ex vivo expanded cord blood cells using the copper chelator tetraethylenepentamine: a phase I/II clinical trial , 2008, Bone Marrow Transplantation.

[40]  F. Appelbaum,et al.  Hematopoietic-cell transplantation at 50. , 2007, The New England journal of medicine.

[41]  J. Klein,et al.  Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study , 2007, The Lancet.

[42]  J. Stockman,et al.  Transplantation of Umbilical-Cord Blood in Babies With Infantile Krabbe's Disease , 2007 .

[43]  B. Yeap,et al.  Double unrelated reduced-intensity umbilical cord blood transplantation in adults. , 2007, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[44]  David D. Smith,et al.  Differentiation of naive cord-blood T cells into CD19-specific cytolytic effectors for posttransplantation adoptive immunotherapy. , 2006, Blood.

[45]  E. Shpall,et al.  Superior ex vivo cord blood expansion following co-culture with bone marrow-derived mesenchymal stem cells , 2006, Bone Marrow Transplantation.

[46]  Todd E DeFor,et al.  Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. , 2005, Blood.

[47]  J. Wagner,et al.  Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. , 2004, The New England journal of medicine.

[48]  M. Labopin,et al.  Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. , 2004, The New England journal of medicine.

[49]  L. Xia,et al.  Surface fucosylation of human cord blood cells augments binding to P-selectin and E-selectin and enhances engraftment in bone marrow. , 2004, Blood.

[50]  A. Nagler,et al.  Pre-clinical development of cord blood-derived progenitor cell graft expanded ex vivo with cytokines and the polyamine copper chelator tetraethylenepentamine. , 2004, Cytotherapy.

[51]  P. Wernet,et al.  A New Human Somatic Stem Cell from Placental Cord Blood with Intrinsic Pluripotent Differentiation Potential , 2004, The Journal of experimental medicine.

[52]  M. Poe,et al.  Cord-blood transplants from unrelated donors in patients with Hurler's syndrome. , 2004, The New England journal of medicine.

[53]  S. Chevret,et al.  Unrelated cord blood transplantation for childhood acute myeloid leukemia: a Eurocord Group analysis. , 2003, Blood.

[54]  J. Wagner,et al.  Rapid and complete donor chimerism in adult recipients of unrelated donor umbilical cord blood transplantation after reduced-intensity conditioning. , 2003, Blood.

[55]  Pingfu Fu,et al.  Augmentation of umbilical cord blood (UCB) transplantation with ex vivo-expanded UCB cells: results of a phase 1 trial using the AastromReplicell System. , 2003, Blood.

[56]  A. McWhinnie,et al.  Unrelated umbilical cord blood transplants in adults: Early recovery of neutrophils by supportive co-transplantation of a low number of highly purified peripheral blood CD34+ cells from an HLA-haploidentical donor. , 2003, Experimental hematology.

[57]  C. Chapman,et al.  Successful umbilical cord blood stem cell transplantation for chronic granulomatous disease , 2003, Bone Marrow Transplantation.

[58]  D. Bodine,et al.  High-efficiency recovery of functional hematopoietic progenitor and stem cells from human cord blood cryopreserved for 15 years , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[59]  Chan Zeng,et al.  Transplantation of ex vivo expanded cord blood. , 2002, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[60]  Todd E DeFor,et al.  Searching for unrelated donor hematopoietic stem cells: availability and speed of umbilical cord blood versus bone marrow. , 2002, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[61]  P. Bolufer,et al.  Standardized, unrelated donor cord blood transplantation in adults with hematologic malignancies. , 2001, Blood.

[62]  C. Verfaillie,et al.  Umbilical cord blood cells capable of engrafting in primary, secondary, and tertiary xenogeneic hosts are preserved after ex vivo culture in a noncontact system. , 2001, Blood.

[63]  C. Hillyer Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical siblingV. Rocha, J.E. Wagner, Jr., K.A. Sobocinski, et al. N Eng J Med 342:1846–1854, 2000 , 2001 .

[64]  I McNiece,et al.  Increased expansion and differentiation of cord blood products using a two-step expansion culture. , 2000, Experimental hematology.

[65]  P. Price,et al.  Prompt and durable engraftment in two older adult patients with high risk chronic myelogenous leukemia (CML) using ex vivo expanded and unmanipulated unrelated umbilical cord blood , 2000, Bone Marrow Transplantation.

[66]  K. Ando,et al.  Ex vivo generation of CD34(+) cells from CD34(-) hematopoietic cells. , 1999, Blood.

[67]  F Locatelli,et al.  Factors associated with outcome after cord blood transplantation in children with acute leukemia. Eurocord-Cord Blood Transplant Group. , 1999, Blood.

[68]  J. Adamson,et al.  Outcomes among 562 recipients of placental-blood transplants from unrelated donors. , 1998, The New England journal of medicine.

[69]  Anajane G. Smith,et al.  Optimizing outcome after unrelated marrow transplantation by comprehensive matching of HLA class I and II alleles in the donor and recipient. , 1998, Blood.

[70]  P. Wernet,et al.  NETCORD: a cord blood allocation network. , 1998, Bone marrow transplantation.

[71]  P. Wernet,et al.  An eight-fold ex vivo expansion of long-term culture-initiating cells from umbilical cord blood in stirred suspension cultures. , 1998, Bone marrow transplantation.

[72]  P. Wernet,et al.  The effect of different thawing methods, growth factor combinations and media on the ex vivo expansion of umbilical cord blood primitive and committed progenitors , 1998, Bone Marrow Transplantation.

[73]  J. Even,et al.  The umbilical cord blood alphabeta T-cell repertoire: characteristics of a polyclonal and naive but completely formed repertoire. , 1998, Blood.

[74]  J. Wagner,et al.  Placental and/or umbilical cord blood: an alternative source of hematopoietic stem cells for transplantation. , 1997, Blood.

[75]  C. Chastang,et al.  Outcome of cord-blood transplantation from related and unrelated donors , 1997 .

[76]  W. Piacibello,et al.  Extensive amplification and self-renewal of human primitive hematopoietic stem cells from cord blood. , 1997, Blood.

[77]  H. Miyazaki,et al.  Thrombopoietin augments ex vivo expansion of human cord blood-derived hematopoietic progenitors in combination with stem cell factor and flt3 ligand , 1997, Leukemia.

[78]  V. Najfeld,et al.  A murine model for human cord blood transplantation: near-term fetal and neonatal peripheral blood cells can achieve long-term bone marrow engraftment in sublethally irradiated adult recipients. , 1997, Blood.

[79]  J. Wagner,et al.  Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: analysis of engraftment and acute graft-versus-host disease. , 1996, Blood.

[80]  V. Barbu,et al.  Cord-blood transplantation from an unrelated donor in an adult with chronic myelogenous leukemia. , 1996, The New England journal of medicine.

[81]  J. Kurtzberg,et al.  Placental blood as a source of hematopoietic stem cells for transplantation into unrelated recipients. , 1996, The New England journal of medicine.

[82]  Thomas O. Toole,et al.  Hematopoietic potential of cryopreserved and ex vivo manipulated umbilical cord blood progenitor cells evaluated in vitro and in vivo. , 1996, Blood.

[83]  A. Anichini,et al.  Massive ex vivo generation of functional dendritic cells from mobilized CD34+ blood progenitors for anticancer therapy. , 1995, Experimental hematology.

[84]  G. Sirchia,et al.  The effect of interleukin‐12 in ex‐vivo expansion of human haemopoietic progenitors , 1995, British journal of haematology.

[85]  K. Tanaka,et al.  Ex vivo expansion of hematopoietic progenitor cells in human cord blood: an effect enhanced by cord blood serum. , 1995, Hematologic pathology.

[86]  E. Thomas Bone Marrow Transplantation—Past, Present and Future , 1994, Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion.

[87]  J. Adamson,et al.  Long-term generation of colony-forming cells (CFC) from CD34+ human umbilical cord blood cells. , 1993, Leukemia & lymphoma.

[88]  J. Kurtzberg,et al.  Hematopoietic reconstitution in a patient with Fanconi's anemia by means of umbilical-cord blood from an HLA-identical sibling. , 1989, The New England journal of medicine.

[89]  H. Broxmeyer,et al.  Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[90]  F. Appelbaum,et al.  Successful engraftment of cryopreserved autologous bone marrow in patients with malignant lymphoma. , 1978, Blood.

[91]  R Storb,et al.  Bone-marrow transplantation (first of two parts). , 1975, The New England journal of medicine.

[92]  R. Blaese,et al.  Long-term remission from acute myelogenous leukemia after bone marrow transplantation and recovery from acute graft-versus-host reaction and prolonged immunoincompetence. , 1975, Blood.

[93]  J. Bull,et al.  Bone-marrow transplantation following combination chemotherapy immunosuppression (B.A.C.T.) in patients with acute leukemia. , 1974, Transplantation proceedings.

[94]  R. Gatti,et al.  Immunological reconstitution of sex-linked lymphopenic immunological deficiency. , 1968, Lancet.

[95]  J. Cannon,et al.  Supralethal whole body irradiation and isologous marrow transplantation in man. , 1959, The Journal of clinical investigation.

[96]  E. Thomas,et al.  Irradiation of the entire body and marrow transplantation: some observations and comments. , 1959, Blood.

[97]  E. Thomas,et al.  Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. , 1957, The New England journal of medicine.

[98]  C. Congdon Experimental treatment of total-body irradiation injury: a brief review. , 1957, Blood.

[99]  E. E. Osgood,et al.  APLASTIC ANEMIA TREATED WITH DAILY TRANSFUSIONS AND INTRAVENOUS MARROW; CASE REPORT , 1939 .