title: Magnetically labeled human natural killer cells, accumulated in vitro by an external magnetic force, are effective against HOS osteosarcoma cells.
abstract: We evaluated the efficacy of a novel natural killer (NK) cell delivery system in vitro, and also investigated the antitumor effect of the accumulated cells on HOS osteosarcoma cells. Human peripheral blood mononuclear cells were isolated and co-cultured with inactivated K562 erythroleukaemic cells in the presence of IL-2 for 5 days. CD3- CD56+ NK cells were labeled with immunomagnetic beads and separated using a magnetic cell sorting system. Purity and cytotoxicity against K562 cells and HOS cells of the magnetically labeled NK cells were measured. To evaluate whether magnetically labeled NK cells could be accumulated in a specific area by magnetic force, the NK cells were placed in chamber slides in the presence, or not, of an external magnetic force of a neodymium magnet (diameter: 1.5 mm, height: 3 mm, total magnetic flux density: 0.282 T). Moreover, to investigate the antitumor effect on HOS cells, the magnetically labeled NK cells were added to HOS cells in chamber slides in the presence, or not, of an external magnetic force for various times. HOS cells were subsequently stained with Papanicolaou for histological examination. It was found that the magnetically labeled NK cells were highly purified and had cytotoxicity against target cells. The NK cells were accumulated effectively by the magnetic field and, when the NK cells were added to HOS cells in a chamber slide with a magnet placed beneath, a significantly larger number of HOS cells detached from the magnet zone than from other zones. Apoptosis was detected in most detached HOS cells. In conclusion, these findings indicate that magnetically accumulated NK cells efficiently induced apoptosis in HOS cells, suggesting that magnetic targeting therapy using magnetically labeled NK cells holds promise as an immunotherapy for osteosarcoma.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan. yukonaka@hiroshima-u.ac.jp
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakashima
authors.forename: Masataka
authors.initials: M
authors.lastname: Deie
authors.forename: Shinobu
authors.initials: S
authors.lastname: Yanada
authors.forename: Patrick
authors.initials: P
authors.lastname: Sharman
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Ochi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D017252:CD3 Complex / Q000096:biosynthesis; D019002:CD56 Antigen / Q000096:biosynthesis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002469:Cell Separation / Q000379:methods*; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000166:cytology* / Q000378:metabolism; D008280:Magnetics; D012516:Osteosarcoma / Q000628:therapy*; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D017252:CD3 Complex; D019002:CD56 Antigen; D007376:Interleukin-2; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases