title: Protective role of functionalized single walled carbon nanotubes enhance ex vivo expansion of hematopoietic stem and progenitor cells in human umbilical cord blood.
abstract: In this study, carboxylic acid functionalized single walled carbon nanotubes (f-SWCNT-COOH) was shown to support the viability and ex vivo expansion of freeze-thawed, non-enriched hematopoietic stem and progenitor cells (HSPC) in human umbilical cord blood-mononucleated cells (UCB-MNC). Our in vitro experiments showed that f-SWCNT-COOH increased the viability of the CD45(+) cells even without cytokine stimulation. It also reduced mitochondrial superoxides and caspase activity in CD45(+) cells. f-SWCNT-COOH drastically reduced the proportions of CD45(-) cells in the non-enriched UCB-MNC. Phenotypic expression analysis and functional colony forming units (CFU) showed significant ex vivo expansion of HSPC, particularly of CD45(+)CD34(+)CD38(-) population and granulocyte-macrophage (GM) colonies, in f-SWCNT-COOH augmented cultures supplemented with basal cytokines. In vivo data suggested that f-SWCNT-COOH expanded UCB-MNC could repopulate immunodeficient mice models with minimal acute or sub-acute symptoms of graft-versus-host disease (GVHD) and f-SWCNT-COOH dependent toxicity.
  
  
  BACKGROUND
  In this paper a novel method is presented by using single wall functionalized carbon nanotubes to enhance viability and ex vivo expansion of freeze-thawed, non-enriched hematopoietic stem and progenitor cells in human umbilical cord blood -mononucleated cells. Detailed data is presented about enhanced viability, including improved repopulation of immunodeficient mice models with minimal acute or sub-acute symptoms of graft-versus-host disease.
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.forename: Pat Pak Yan
authors.initials: PP
authors.lastname: Chu
authors.forename: Andrea
authors.initials: A
authors.lastname: Lim
authors.forename: Xiubo
authors.initials: X
authors.lastname: Fan
authors.forename: Florence Pik Hoon
authors.initials: FP
authors.lastname: Gay
authors.forename: Ralph Milford
authors.initials: RM
authors.lastname: Bunte
authors.forename: Tony Kiat Hon
authors.initials: TK
authors.lastname: Lim
authors.forename: Shang
authors.initials: S
authors.lastname: Li
authors.forename: Gigi Ngar Chee
authors.initials: GN
authors.lastname: Chiu
authors.forename: William Ying Khee
authors.initials: WY
authors.lastname: Hwang
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D002264:Carboxylic Acids / Q000737:chemistry; D018929:Cell Culture Techniques / Q000379:methods; D002470:Cell Survival; D005312:Fetal Blood / Q000166:cytology* / Q000637:transplantation*; D005615:Freezing; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D051379:Mice; D016513:Mice, SCID; D037742:Nanotubes, Carbon / Q000737:chemistry*
chemical_list: D018952:Antigens, CD34; D002264:Carboxylic Acids; D037742:Nanotubes, Carbon; D017493:Leukocyte Common Antigens; D051997:ADP-ribosyl Cyclase 1
keywords: CCD; CD; CFU; CFU-GEMM; CFU-GM; CLP; CMP; CNT; Carbon Nanotubes; Carboxylic Acid Functionalized Single-Walled Carbon Nanotube; Charge-Couple Device; Cluster of Differentiation; Colony Forming Unit-Granulocyte, Erythorcyte, Macrophage, Monocyte; Colony Forming Unit-Granulocyte, Macrophage; Colony Forming Units; Common Lymphoid Progenitors; Common Myeloid Progenitors; DMSO; DPBS; Dimethyl Sulfoxide; Dulbecco's Phosphate Buffered Saline; Ex Vivo Expansion of UCB; FLICA; FLT-3; FLT-3 Ligand; FS; Fluorescent Labeled Inhibitor of Caspases; Forward Scatter; Functionalized Single Walled Carbon Nanotubes (f-SWNCT); Functionalized Single-Walled Carbon Nanotubes; GVHD; Graft-Versus-Host Disease; H&E; HPC; HSC; HSCT; HSPC; Hematopoietic Progenitor Cells; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cell Transplantation (HSCT); Hematopoietic Stem Cells; Hematopoietic Stem and Progenitor Cells; Hematoxylin and Eosin; IACUC; IGFBP-2; Immunodeficient Mouse Model; Institutional Animal Care and Use Committee; Insulin-Like Growth Factor Binding Protein-2; MNC; MSC; MW; Mesenchymal Stem/Stromal Cells; Mononucleated/Mononuclear Cells; Multi-Walled; NK; NOD; NOD SCID Gamma; NSG; Natural Killer; Non-Obese Diabetic; PLT; Platelet; RBC; ROS; Reactive Oxygen Species; Red Blood Cell; SCF; SCID; SCID Repopulating Capacity/Cell; SEM; SRC; SS; SW; Severe Combined Immunodeficiency; Side Scatter; Single-Walled; Standard Error of the Mean; Stem Cell Factor; TNC; TPO; Thrombopoietin; Total Nucleated Cells; UCB; UCB-MNC; UCBT; Umbilical Cord Blood; Umbilical Cord Blood (UCB); Umbilical Cord Blood Transplantation; Umbilical Cord Blood-Mononucleated Cells; VLA-4; Very Late Antigen-4; WBC; White Blood Cell; f-SWCNT; f-SWCNT-COOH