Natural killer cells improve hematopoietic stem cell engraftment by increasing stem cell clonogenicity in vitro and in a humanized mouse model
Escobedo-Cousin, M. (University College London)
Jackson, N. (Anthony Nolan Research Institute)
Laza-Briviesca, Raquel (Anthony Nolan Research Institute)
Ariza-McNaughton, L. (London Research Institute)
Luevano, M. (Anthony Nolan Research Institute)
Derniame, S. (Anthony Nolan Research Institute)
Querol, Sergi (Banc de Sang i Teixits (Barcelona, Catalunya))
Blundell, M. (University College London)
Thrasher, A. (University College London)
Soria, B. (Instituto de Salud Carlos III)
Cooper, N. (Hammersmith Hospital (Londres))
Bonnet, D. (London Research Institute)
Madrigal, A. (Anthony Nolan Research Institute)
Saudemont, A. (Anthony Nolan Research Institute)
Universitat Autònoma de Barcelona

Data:	2015
Resum:	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. Copyright:.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	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
Publicat a:	PloS one, Vol. 10 Núm. 10 (14 2015) , p. e0138623, ISSN 1932-6203

DOI: 10.1371/journal.pone.0138623
PMID: 26465138

16 p, 1.9 MB

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