Escobedo-Cousin, MichelleJackson, NicolaLaza-Briviesca, RaquelAriza-McNaughton, LindaLuevano, MarthaDerniame, SophieQuerol, SergioBlundell, MichaelThrasher, AdrianSoria, BernatCooper, NicholaBonnet, DominiqueMadrigal, AlejandroSaudemont, Aurore2016-07-042016-07-042015Escobedo-Cousin M, Jackson N, Laza-Briviesca R, Ariza-McNaughton L, Luevano M, Derniame S, et al. Natural Killer Cells Improve Hematopoietic Stem Cell Engraftment by Increasing Stem Cell Clonogenicity In Vitro and in a Humanized Mouse Model. PLoS ONE; 10(10):e0138623http://hdl.handle.net/10668/2248Journal Article; Research Support, Non-U.S. Gov't;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.enNK cellsHematopoietic stem cellsMouse modelsIntegrinsT cellsGene expressionFlow cytometryCytotoxic T cellsCélulas Asesinas NaturalesCélulas Madre HematopoyéticasCélulas Madre Embrionarias de RatonesIntegrinasExpresión GénicaCitometría de flujoMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell MovementMedical Subject Headings::Chemicals and Drugs::Biological Factors::Chemotactic Factors::Chemokines::Chemokines, CXC::Chemokine CXCL9Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Cell Transplantation::Stem Cell Transplantation::Cord Blood Stem Cell TransplantationMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Cycle::Cell Division::CytokinesisMedical Subject Headings::Anatomy::Embryonic Structures::Fetus::Fetal BloodMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression RegulationMedical Subject Headings::Diseases::Immune System Diseases::Graft vs Host DiseaseMedical Subject Headings::Phenomena and Processes::Immune System Phenomena::Immune System Processes::Transplantation Immunology::Graft vs Host Reaction::Graft vs Tumor Effect::Graft vs Leukemia EffectMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Cell Transplantation::Stem Cell Transplantation::Hematopoietic Stem Cell TransplantationMedical Subject Headings::Anatomy::Hemic and Immune Systems::Hematopoietic System::Bone Marrow Cells::Hematopoietic Stem CellsMedical Subject Headings::Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins::Interleukin-15Medical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Killer Cells, NaturalMedical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, MononuclearMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Inbred Strains::Mice, Inbred NODMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Mutant Strains::Mice, SCIDMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Hybridization::Oligonucleotide Array Sequence AnalysisMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Recombinant ProteinsMedical Subject Headings::Anatomy::Cells::Stem CellsAnimalsresearch article26465138open access10.1371/journal.pone.01386231932-6203PMC4605799