{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:57:18Z","timestamp":1785419838789,"version":"3.56.0"},"reference-count":33,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T00:00:00Z","timestamp":1688169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["21-75-10147"],"award-info":[{"award-number":["21-75-10147"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Science and Higher Education of the Russian Federation for RCMG","award":["21-75-10147"],"award-info":[{"award-number":["21-75-10147"]}]},{"name":"NRC Kurchatov Institute","award":["21-75-10147"],"award-info":[{"award-number":["21-75-10147"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Adenovirus-mediated gene therapy is a promising tool in bone regenerative medicine. In this work, gene-activated matrices (GAMs) composed of (1) polylactide granules (PLA), which serve as a depot for genetic constructs or matrices for cell attachment, (2) a PRP-based fibrin clot, which is a source of growth factors and a binding gel, and (3) a BMP2 gene providing osteoinductive properties were studied. The study aims to compare the effectiveness of in vivo and ex vivo gene therapy based on adenoviral constructs with the BMP2 gene, PLA particles, and a fibrin clot for bone defect healing. GAMs with Ad-BMP2 and MSC(Ad-BMP2) show osteoinductive properties both in vitro and in vivo. However, MSCs incubated with GAMs containing transduced cells showed a more significant increase in osteopontin gene expression, protein production, Alpl activity, and matrix mineralization. Implantation of the studied matrices into critical-size calvarial defects after 56 days promotes the formation of young bone. The efficiency of neoosteogenesis and the volume fraction of newly formed bone tissue are higher with PLA\/PRP-MSC(Ad-BMP2) implantation (33%) than PLA\/PRP-Ad-BMP2 (28%). Thus, ex vivo adenoviral gene therapy with the BMP2 gene has proven to be a more effective approach than the in vivo delivery of gene constructs for bone regeneration.<\/jats:p>","DOI":"10.3390\/cells12131762","type":"journal-article","created":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T00:34:08Z","timestamp":1688344448000},"page":"1762","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Adenovirus-Based Gene Therapy for Bone Regeneration: A Comparative Analysis of In Vivo and Ex Vivo BMP2 Gene Delivery"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0481-256X","authenticated-orcid":false,"given":"Tatiana Borisovna","family":"Bukharova","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, 115478 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8472-7116","authenticated-orcid":false,"given":"Irina Alekseevna","family":"Nedorubova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115478 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktoria Olegovna","family":"Mokrousova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115478 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasiia Yurevna","family":"Meglei","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115478 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktoriia Pavlovna","family":"Basina","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115478 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5915-7999","authenticated-orcid":false,"given":"Andrey Anatolevich","family":"Nedorubov","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine and Biotechnology and E.V. Borovsky Institute of Dentistry, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7169-2724","authenticated-orcid":false,"given":"Andrey Vyacheslavovich","family":"Vasilyev","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115478 Moscow, Russia"},{"name":"Institute of Translational Medicine and Biotechnology and E.V. Borovsky Institute of Dentistry, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timofei Evgenevich","family":"Grigoriev","sequence":"additional","affiliation":[{"name":"NRC \u201cKurchatov Institute\u201d, 123182 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuriy Dmitrievich","family":"Zagoskin","sequence":"additional","affiliation":[{"name":"NRC \u201cKurchatov Institute\u201d, 123182 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei Nicolaevich","family":"Chvalun","sequence":"additional","affiliation":[{"name":"NRC \u201cKurchatov Institute\u201d, 123182 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey Ivanovich","family":"Kutsev","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115478 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry Vadimovich","family":"Goldshtein","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115478 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hosseinkhani, H., Domb, A.J., Sharifzadeh, G., and Nahum, V. 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