10779/crick.12681857.v1
Michelle Escobedo-Cousin
Michelle
Escobedo-Cousin
Nicola Jackson
Nicola
Jackson
Raquel Laza-Briviesca
Raquel
Laza-Briviesca
Linda Ariza-McNaughton
Linda
Ariza-McNaughton
Martha Luevano
Martha
Luevano
Sophie Derniame
Sophie
Derniame
Sergio Querol
Sergio
Querol
Michael Blundell
Michael
Blundell
Adrian Thrasher
Adrian
Thrasher
Bernat Soria
Bernat
Soria
Nichola Cooper
Nichola
Cooper
Dominique Bonnet
Dominique
Bonnet
Alejandro Madrigal
Alejandro
Madrigal
Aurore Saudemont
Aurore
Saudemont
Natural killer cells improve hematopoietic stem cell engraftment by increasing stem cell clonogenicity in vitro and in a humanized mouse model
The Francis Crick Institute
2020
Animals
Cell Movement
Chemokine CXCL9
Cord Blood Stem Cell Transplantation
Cytokines
Female
Fetal Blood
Gene Expression Regulation
Graft vs Host Disease
Graft vs Leukemia Effect
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells
Humans
Interleukin-15
Killer Cells, Natural
Leukocytes, Mononuclear
Male
Mice
Mice, Inbred NOD
Mice, SCID
Oligonucleotide Array Sequence Analysis
Recombinant Proteins
Stem Cells
Bonnet
General Science & Technology
2020-07-21 11:03:47
Journal contribution
https://crick.figshare.com/articles/journal_contribution/Natural_killer_cells_improve_hematopoietic_stem_cell_engraftment_by_increasing_stem_cell_clonogenicity_in_vitro_and_in_a_humanized_mouse_model/12681857
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.