title: Expansion and homing of umbilical cord blood hematopoietic stem and progenitor cells for clinical transplantation.
abstract: The successful expansion of hematopoietic stem and progenitor cells (HSPCs) from umbilical cord blood (UCB) for transplantation could revolutionize clinical practice by improving transplantation-related outcomes and making available UCB units that have suboptimal cell doses for transplantation. New cytokine combinations appear able to promote HSPC growth with minimal differentiation into mature precursors and new agents, such as insulin-like growth factor-binding protein 2, are being used in clinical trials. Molecules that simulate the HSPC niche, such as Notch ligand, have also shown promise. Further improvements have been made with the use of mesenchymal stromal cells, which have made possible UCB expansion without a potentially deleterious prior CD34/CD133 cell selection step. Chemical molecules, such as copper chelators, nicotinamide, and aryl hydrocarbon antagonists, have shown excellent outcomes in clinical studies. The use of bioreactors could further add to HSPC studies in future. Drugs that could improve HSPC homing also appear to have potential in improving engraftment times in UCB transplantation. Technologies to expand HSPC from UCB and to enhance the homing of these cells appear to have attained the goal of accelerating hematopoietic recovery. Further discoveries and clinical studies are likely to make the goal of true HSPC expansion a reality for many applications in future.
authors.affiliation: Department of Hematology, Singapore General Hospital, Singapore; Department of Pharmacy, National University of Singapore, Singapore.
authors.forename: Sudipto
authors.initials: S
authors.lastname: Bari
authors.affiliation: Sydney Medical School, The University of Sydney, Australia.
authors.forename: Kevin Kwee Hong
authors.initials: KK
authors.lastname: Seah
authors.affiliation: BioSystems and Micromechanics, Singapore-MIT Alliance for Research and Technology, Singapore.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Poon
authors.affiliation: Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Alice Man Sze
authors.initials: AM
authors.lastname: Cheung
authors.affiliation: Department of Clinical Research, Singapore General Hospital, Singapore.
authors.forename: Xiubo
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Hematology, Singapore General Hospital, Singapore.
authors.forename: Shin-Yeu
authors.initials: SY
authors.lastname: Ong
authors.affiliation: Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Shang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Hematology-Oncology, National University Cancer Institute, Singapore.
authors.forename: Liang Piu
authors.initials: LP
authors.lastname: Koh
authors.affiliation: Department of Hematology, Singapore General Hospital, Singapore; Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore; Singapore Cord Blood Bank, Singapore. Electronic address: william.hwang.y.k@sgh.com.sg.
authors.forename: William Ying Khee
authors.initials: WY
authors.lastname: Hwang
mesh_terms: D019149:Bioreactors; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002986:Clinical Trials as Topic; D036101:Cord Blood Stem Cell Transplantation; D016207:Cytokines / Q000494:pharmacology; D005029:Ethylenediamines / Q000494:pharmacology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology; D008565:Membrane Proteins / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D009536:Niacinamide / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors / Q000276:immunology; D055153:Stem Cell Niche / Q000276:immunology*
chemical_list: D016207:Cytokines; D005029:Ethylenediamines; C577903:IGFBP2 protein, human; D018971:Insulin-Like Growth Factor Binding Protein 2; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018336:Receptors, Aryl Hydrocarbon; C064045:delta protein; D009536:Niacinamide; C034269:tetraethylenepentamine
keywords: Clinical trials; Engraftment; Ex vivo expansion; Hematopoietic stem and progenitor cells; Hematopoietic stem cell transplantation; Umbilical cord blood