{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T06:01:04Z","timestamp":1782453664973,"version":"3.54.5"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T00:00:00Z","timestamp":1675036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003243","name":"Ministry of Health of the Czech Republic","doi-asserted-by":"publisher","award":["NU21-03-00032"],"award-info":[{"award-number":["NU21-03-00032"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Myeloma bone disease (MBD) is one of the major complications in multiple myeloma (MM)\u2014the second most frequent hematologic malignancy. It is characterized by the formation of bone lesions due to the local action of proliferating MM cells, and to date, no effective therapy has been developed. In this study, we propose a novel approach for the local treatment of MBD with a combination of natural killer cells (NKs) and mesenchymal stem cells (MSCs) within a fibrin scaffold, altogether known as FINM. The unique biological properties of the NKs and MSCs, joined to the injectable biocompatible fibrin, permitted to obtain an efficient \u201coff-the-shelf\u201d ready-to-use composite for the local treatment of MBD. Our in vitro analyses demonstrate that NKs within FINM exert a robust anti-tumor activity against MM cell lines and primary cells, with the capacity to suppress osteoclast activity (~60%) within in vitro 3D model of MBD. Furthermore, NKs\u2019 post-thawing cytotoxic activity is significantly enhanced (~75%) in the presence of MSCs, which circumvents the decrease of NKs cytotoxicity after thawing, a well-known issue in the cryopreservation of NKs. To reduce the tumor escape, we combined FINM with other therapeutic agents (bortezomib (BZ), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)), observing a clear therapeutic synergistic effect in vitro. Finally, the therapeutic efficacy of FINM in combination with BZ and TRAIL was assessed in a mouse model of MM, achieving 16-fold smaller tumors compared to the control group without treatment. These results suggest the potential of FINM to serve as an allogeneic \u201coff-the-shelf\u201d approach to improve the outcomes of patients suffering from MBD.<\/jats:p>","DOI":"10.3390\/cells12030448","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T07:56:48Z","timestamp":1675065408000},"page":"448","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel Local \u201cOff-the-Shelf\u201d Immunotherapy for the Treatment of Myeloma Bone Disease"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6378-4696","authenticated-orcid":false,"given":"Sandra","family":"Charv\u00e1tov\u00e1","sequence":"first","affiliation":[{"name":"Department of Haematooncology, Faculty of Medicine, University of Ostrava, 70300 Ostrava, Czech Republic"},{"name":"Faculty of Science, University of Ostrava, 70100 Ostrava, Czech Republic"},{"name":"Department of Haematooncology, University Hospital Ostrava, 70800 Ostrava, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2549-0918","authenticated-orcid":false,"given":"Benjamin","family":"Motais","sequence":"additional","affiliation":[{"name":"Department of Haematooncology, Faculty of Medicine, University of Ostrava, 70300 Ostrava, Czech Republic"},{"name":"Faculty of Science, University of Ostrava, 70100 Ostrava, Czech Republic"},{"name":"Department of Haematooncology, University Hospital Ostrava, 70800 Ostrava, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justyna","family":"Czapla","sequence":"additional","affiliation":[{"name":"Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44102 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Cicho\u0144","sequence":"additional","affiliation":[{"name":"Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44102 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1131-289X","authenticated-orcid":false,"given":"Ryszard","family":"Smolarczyk","sequence":"additional","affiliation":[{"name":"Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44102 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Walek","sequence":"additional","affiliation":[{"name":"Department of Haematooncology, Faculty of Medicine, University of Ostrava, 70300 Ostrava, Czech Republic"},{"name":"Department of Haematooncology, University Hospital Ostrava, 70800 Ostrava, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Giebel","sequence":"additional","affiliation":[{"name":"Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44102 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"H\u00e1jek","sequence":"additional","affiliation":[{"name":"Department of Haematooncology, Faculty of Medicine, University of Ostrava, 70300 Ostrava, Czech Republic"},{"name":"Department of Haematooncology, University Hospital Ostrava, 70800 Ostrava, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2862-4048","authenticated-orcid":false,"given":"Juli R.","family":"Bag\u00f3","sequence":"additional","affiliation":[{"name":"Department of Haematooncology, Faculty of Medicine, University of Ostrava, 70300 Ostrava, Czech Republic"},{"name":"Department of Haematooncology, University Hospital Ostrava, 70800 Ostrava, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21332","article-title":"Cancer statistics","volume":"66","author":"Siegel","year":"2016","journal-title":"CA Cancer J Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/leu.2013.313","article-title":"Continued improvement in survival in multiple myeloma: Changes in early mortality and outcomes in older patients","volume":"28","author":"Kumar","year":"2014","journal-title":"Leukemia"},{"key":"ref_3","first-page":"28","article-title":"Bone disease in multiple 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