title: A Novel High-Throughput Screening Platform Reveals an Optimized Cytokine Formulation for Human Hematopoietic Progenitor Cell Expansion.
abstract: The main limitations of hematopoietic cord blood (CB) transplantation, viz, low cell dosage and delayed reconstitution, can be overcome by ex vivo expansion. CB expansion under conventional culture causes rapid cell differentiation and depletion of hematopoietic stem and progenitor cells (HSPCs) responsible for engraftment. In this study, we use combinatorial cell culture technology (CombiCult®) to identify medium formulations that promote CD133+CB HSPC proliferation while maintaining their phenotypic characteristics. We employed second-generation CombiCult screens that use electrospraying technology to encapsulate CB cells in alginate beads. Our results suggest that not only the combination but also the order of addition of individual components has a profound influence on expansion of specific HSPC populations. Top protocols identified by the CombiCult screen were used to culture human CD133+CB HSPCs on nanofiber scaffolds and validate the expansion of the phenotypically defined CD34+CD38lo/-CD45RA-CD90+CD49f+population of hematopoietic stem cells and their differentiation into defined progeny.
authors.affiliation: 1 Plasticell Ltd. , Stevenage Bioscience Catalyst, Stevenage, United Kingdom.
authors.forename: Marina
authors.initials: M
authors.lastname: Tarunina
authors.affiliation: 1 Plasticell Ltd. , Stevenage Bioscience Catalyst, Stevenage, United Kingdom.
authors.forename: Diana
authors.initials: D
authors.lastname: Hernandez
authors.affiliation: 2 Stem Cell Research, Nuffield Division of Clinical Laboratory Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford , Oxford, United Kingdom .|3 Stem Cell Research, NHS Blood and Transplant, Radcliffe Department of Medicine, John Radcliffe Hospital , Oxford, United Kingdom .
authors.forename: Barbara
authors.initials: B
authors.lastname: Kronsteiner-Dobramysl
authors.affiliation: 4 Department of Surgery and Cancer, Faculty of Medicine, Imperial College London , South Kensington, United Kingdom .
authors.forename: Philip
authors.initials: P
authors.lastname: Pratt
authors.affiliation: 1 Plasticell Ltd. , Stevenage Bioscience Catalyst, Stevenage, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Watson
authors.affiliation: 2 Stem Cell Research, Nuffield Division of Clinical Laboratory Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford , Oxford, United Kingdom .|3 Stem Cell Research, NHS Blood and Transplant, Radcliffe Department of Medicine, John Radcliffe Hospital , Oxford, United Kingdom .
authors.forename: Peng
authors.initials: P
authors.lastname: Hua
authors.affiliation: 2 Stem Cell Research, Nuffield Division of Clinical Laboratory Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford , Oxford, United Kingdom .|3 Stem Cell Research, NHS Blood and Transplant, Radcliffe Department of Medicine, John Radcliffe Hospital , Oxford, United Kingdom .
authors.forename: Francesca
authors.initials: F
authors.lastname: Gullo
authors.affiliation: 2 Stem Cell Research, Nuffield Division of Clinical Laboratory Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford , Oxford, United Kingdom .|3 Stem Cell Research, NHS Blood and Transplant, Radcliffe Department of Medicine, John Radcliffe Hospital , Oxford, United Kingdom .
authors.forename: Mark
authors.initials: M
authors.lastname: van der Garde
authors.affiliation: 2 Stem Cell Research, Nuffield Division of Clinical Laboratory Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford , Oxford, United Kingdom .|3 Stem Cell Research, NHS Blood and Transplant, Radcliffe Department of Medicine, John Radcliffe Hospital , Oxford, United Kingdom .
authors.forename: Youyi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 1 Plasticell Ltd. , Stevenage Bioscience Catalyst, Stevenage, United Kingdom.
authors.forename: Lilian
authors.initials: L
authors.lastname: Hook
authors.affiliation: 1 Plasticell Ltd. , Stevenage Bioscience Catalyst, Stevenage, United Kingdom.
authors.forename: Yen
authors.initials: Y
authors.lastname: Choo
authors.affiliation: 2 Stem Cell Research, Nuffield Division of Clinical Laboratory Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford , Oxford, United Kingdom .|3 Stem Cell Research, NHS Blood and Transplant, Radcliffe Department of Medicine, John Radcliffe Hospital , Oxford, United Kingdom .
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Watt
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism; D000464:Alginates / Q000494:pharmacology; D000465:Algorithms; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D005434:Flow Cytometry; D020723:Glucuronic Acid / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006603:Hexuronic Acids / Q000494:pharmacology; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D008863:Microspheres; D057139:Nanofibers / Q000737:chemistry; D015203:Reproducibility of Results; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D000071916:AC133 Antigen; D000464:Alginates; D016207:Cytokines; D006603:Hexuronic Acids; D020723:Glucuronic Acid
keywords: CombiCult; alginate encapsulation; ex-vivo expansion; hematopoietic stem/progenitor cells; high-throughput-screening