title: Mitochondrial superoxide reduction and cytokine secretion skewing by carbon nanotube scaffolds enhance ex vivo expansion of human cord blood hematopoietic progenitors.
abstract: In this study, we report that surface functional groups of single walled carbon nanotubes (f-SWCNT) are critical for mediating survival and ex vivo expansion of hematopoietic stem and progenitor cells (HSPC) in human umbilical cord blood (UCB). In comparison to amide (-O-NH2) and polyethylene-glycol (-PEG) functionalized SWCNT, carboxylic acid (-COOH) variants gave optimal viability support which correlated with maximal reduction of lethal mitochondrial superoxides in HSPC. Cytokine array illustrated that f-SWCNT-COOH maintained higher proportion of HSPC associated cytokines and minimal level of differentiation promoting factors. Transplantation of f-SWCNT-COOH expanded grafts in sub-lethally irradiated immunodeficient mice resulted in higher engraftment of HSPC in bone marrow compared to control when they were co-transplanted with non-expanded cells from the same UCB. Expanded grafts mediated higher survival rate of mice compared to non-expanded grafts due to lower graft-versus-host-disease which is likely a consequence of proportion of immune cells in the grafts.
  
  
  BACKGROUND
  Umbilical cord blood (UCB) is a potential source of hematopoietic stem and progenitor (HSPC) cells. One major hurdle for its clinical use is the insufficient yield of cell number. The authors in this study elegantly demonstrated the importance of various functional groups on single-walled carbon nanotubes (f-SWCNT) in enhancing ex vivo expansion of HSPC in UCB. The findings may pave a way for having UCB as a source for HSPC for clinical use in the future.
authors.affiliation: Department of Pharmacy, National University of Singapore, Singapore; Department of Hematology, Singapore General Hospital, Singapore.
authors.forename: Sudipto
authors.initials: S
authors.lastname: Bari
authors.affiliation: Singapore Cord Blood Bank, Singapore.
authors.forename: Pat Pak Yan
authors.initials: PP
authors.lastname: Chu
authors.affiliation: Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lim
authors.affiliation: Department of Clinical Research, Singapore General Hospital, Singapore.
authors.forename: Xiubo
authors.initials: X
authors.lastname: Fan
authors.affiliation: Office of Research, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Ralph Milford
authors.initials: RM
authors.lastname: Bunte
authors.affiliation: Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Shang
authors.initials: S
authors.lastname: Li
authors.affiliation: Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School, Singapore; Center for Computational Biology, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Sujoy
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Pharmacy, National University of Singapore, Singapore. Electronic address: phacncg@nus.edu.sg.
authors.forename: Gigi Ngar Chee
authors.initials: GN
authors.lastname: Chiu
authors.affiliation: Singapore Cord Blood Bank, Singapore; Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore; Department of Hematology, Singapore General Hospital, Singapore. Electronic address: william.hwang.y.k@sgh.com.sg.
authors.forename: William Ying Khee
authors.initials: WY
authors.lastname: Hwang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005312:Fetal Blood / Q000187:drug effects; D006086:Graft vs Host Disease / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D037742:Nanotubes, Carbon / Q000009:adverse effects / Q000737:chemistry*; D013481:Superoxides / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D016207:Cytokines; D037742:Nanotubes, Carbon; D013481:Superoxides
keywords: Ex vivo expansion of UCB; Hematopoietic stem cell transplantation (HSCT); Immunodeficient mouse model; Surface functionalized single walled carbon nanotubes (f-SWNCT); Umbilical cord blood (UCB)