title: Methods of ex vivo expansion of human cord blood cells: challenges, successes and clinical implications.
abstract: More than 40,000 unrelated cord blood transplantations (UCBT) have been performed worldwide as treatment for patients with malignant or non-malignant life threatening hematologic disorders. However, low absolute numbers of hematopoietic stem and progenitor cells (HSPCs) within a single cord blood unit has remained a limiting factor for this transplantation modality, particularly in adult recipients. Further, because UCB contains low numbers of mostly naïve T cells, immune recovery after UCBT is slow, predisposing patients to severe infections. Other causes of UCBT failure has included graft-versus-host disease (GVHD) and relapse of the underlying disease. In this article, we first review the current landscape of cord blood engineering aimed at improving engraftment. This includes approaches of UCB-HSPCs expansion and methods aimed at improving UCB-HSCPs homing. We then discuss recent approaches of cord blood engineering developed to prevent infection [generation of multivirus-specific cytotoxic T cells (VSTs) from UCB], relapse [transduction of UCB-T cells with tumor-specific chimeric receptor antigens (CARs)] and GVHD (expansion of regulatory T cells from UCB). Although many of these techniques of UCB engineering remain currently technically challenging and expensive, they are likely to revolutionize the field of UCBT in the next decades.
authors.affiliation: a Division of Hematology, Department of Medicine , University and CHU of Liège , Liège , Belgium.|b GIGA-I3, Section of Hematology , University of Liège , Liège , Belgium.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Baron
authors.affiliation: c Eurocord Hospital Saint Louis, AP-HP , Paris , France.|d Hospital Saint Antoine , Service d'Hématologie et Thérapie Cellulaire, AP-HP , Paris , France.|e Cord Blood Committee, Cellular Therapy and Immunobiology Working Party , EBMT , Leiden , Netherlands.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Ruggeri
authors.affiliation: f Division of Hematology and Bone Marrow Transplantation , The Chaim Sheba Medical Center, Tel-Hashomer , Ramat-Gan , Israel.|g EBMT Paris Office , Hospital Saint Antoine , Paris , France.|h Université Pierre et Marie Curie , Paris , France.|i Tel Aviv University (TAU) , Tel Aviv , Israel.
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D060846:Cell Engineering / Q000379:methods; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology / Q000637:transplantation*; D006086:Graft vs Host Disease / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology
keywords: HSPC; UCB; Umbilical cord blood; chimeric receptor antigen; cytotoxic T cells; engraftment; expansion; graft-versus-host disease; homing; regulatory T cells; transplantation