Natural killer cells improve hematopoietic stem cell engraftment by increasing stem cell clonogenicity in vitro and in a humanized mouse model
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...
| Autores: | , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:296546 |
| Acceso en línea: | https://ddd.uab.cat/record/296546 https://dx.doi.org/urn:doi:10.1371/journal.pone.0138623 |
| Access Level: | acceso abierto |
| Palabra clave: | 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 |
| Sumario: | 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:. |
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