Natural killer cells improve hematopoietic stem cell engraftment by increasing stem cell clonogenicity in vitro and in a humanized mouse model
journal contributionposted on 21.07.2020, 11:03 authored by Michelle Escobedo-Cousin, Nicola Jackson, Raquel Laza-Briviesca, Linda Ariza-McNaughton, Martha Luevano, Sophie Derniame, Sergio Querol, Michael Blundell, Adrian Thrasher, Bernat Soria, Nichola Cooper, Dominique Bonnet, Alejandro Madrigal, Aurore Saudemont
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.
AnimalsCell MovementChemokine CXCL9Cord Blood Stem Cell TransplantationCytokinesFemaleFetal BloodGene Expression RegulationGraft vs Host DiseaseGraft vs Leukemia EffectHematopoietic Stem Cell TransplantationHematopoietic Stem CellsHumansInterleukin-15Killer Cells, NaturalLeukocytes, MononuclearMaleMiceMice, Inbred NODMice, SCIDOligonucleotide Array Sequence AnalysisRecombinant ProteinsStem CellsBonnetGeneral Science & Technology