title: Natural Killer Cells Improve Hematopoietic Stem Cell Engraftment by Increasing Stem Cell Clonogenicity In Vitro and in a Humanized Mouse Model.
abstract: Cord blood (CB) is increasingly used as a source of hematopoietic stem cells (HSC) for transplantation. Low incidence and severity of graft-versus-host disease (GvHD) and a robust graft-versus-leukemia (GvL) effect are observed following CB transplantation (CBT). However, its main disadvantages are a limited number of HSC per unit, delayed immune reconstitution and a higher incidence of infection. Unmanipulated grafts contain accessory cells that may facilitate HSC engraftment. Therefore, the effects of accessory cells, particularly natural killer (NK) cells, on human CB HSC (CBSC) functions were assessed in vitro and in vivo. CBSC cultured with autologous CB NK cells showed higher levels of CXCR4 expression, a higher migration index and a higher number of colony forming units (CFU) after short-term and long-term cultures. We found that CBSC secreted CXCL9 following interaction with CB NK cells. In addition, recombinant CXCL9 increased CBSC clonogenicity, recapitulating the effect observed of CB NK cells on CBSC. Moreover, the co-infusion of CBSC with CB NK cells led to a higher level of CBSC engraftment in NSG mouse model. The results presented in this work offer the basis for an alternative approach to enhance HSC engraftment that could improve the outcome of CBT.
authors.affiliation: University College London, Cancer Institute, London, United Kingdom; Anthony Nolan Research Institute, Royal Free Campus, London, United Kingdom.
authors.forename: Michelle
authors.initials: M
authors.lastname: Escobedo-Cousin
authors.affiliation: Anthony Nolan Research Institute, Royal Free Campus, London, United Kingdom.
authors.forename: Nicola
authors.initials: N
authors.lastname: Jackson
authors.affiliation: Anthony Nolan Research Institute, Royal Free Campus, London, United Kingdom.
authors.forename: Raquel
authors.initials: R
authors.lastname: Laza-Briviesca
authors.affiliation: Cancer Research UK, London Research Institute, London, United Kingdom.
authors.forename: Linda
authors.initials: L
authors.lastname: Ariza-McNaughton
authors.affiliation: University College London, Cancer Institute, London, United Kingdom; Anthony Nolan Research Institute, Royal Free Campus, London, United Kingdom.
authors.forename: Martha
authors.initials: M
authors.lastname: Luevano
authors.affiliation: University College London, Cancer Institute, London, United Kingdom; Anthony Nolan Research Institute, Royal Free Campus, London, United Kingdom.
authors.forename: Sophie
authors.initials: S
authors.lastname: Derniame
authors.affiliation: Programa Concordia Banc de Sang i Teixits, Barcelona, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Querol
authors.affiliation: University College London, Institute of Child Health, London, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Blundell
authors.affiliation: University College London, Institute of Child Health, London, United Kingdom.
authors.forename: Adrian
authors.initials: A
authors.lastname: Thrasher
authors.affiliation: Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), Fundación Progreso y Salud, Seville, Spain; Biomedical Research Network on Diabetes and Related Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Bernat
authors.initials: B
authors.lastname: Soria
authors.affiliation: Haematology Department, Hammersmith Hospital, London, United Kingdom.
authors.forename: Nichola
authors.initials: N
authors.lastname: Cooper
authors.affiliation: Cancer Research UK, London Research Institute, London, United Kingdom.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnet
authors.affiliation: University College London, Cancer Institute, London, United Kingdom; Anthony Nolan Research Institute, Royal Free Campus, London, United Kingdom.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Madrigal
authors.affiliation: University College London, Cancer Institute, London, United Kingdom; Anthony Nolan Research Institute, Royal Free Campus, London, United Kingdom.
authors.forename: Aurore
authors.initials: A
authors.lastname: Saudemont
mesh_terms: D000818:Animals; D002465:Cell Movement; D054370:Chemokine CXCL9 / Q000378:metabolism; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D005786:Gene Expression Regulation; D006086:Graft vs Host Disease / Q000503:physiopathology; D020544:Graft vs Leukemia Effect; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D020411:Oligonucleotide Array Sequence Analysis; D011994:Recombinant Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*
chemical_list: C080810:CXCL9 protein, human; D054370:Chemokine CXCL9; C485969:Cxcl9 protein, mouse; D016207:Cytokines; C569274:IL15 protein, human; D019409:Interleukin-15; D011994:Recombinant Proteins