Adenovirus-Based Gene Therapy for Bone Regeneration: A Comparative Analysis of In Vivo and Ex Vivo <i>BMP2</i> Gene Delivery
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 o...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-07-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/12/13/1762 |
| _version_ | 1797592030303485952 |
|---|---|
| author | Tatiana Borisovna Bukharova Irina Alekseevna Nedorubova Viktoria Olegovna Mokrousova Anastasiia Yurevna Meglei Viktoriia Pavlovna Basina Andrey Anatolevich Nedorubov Andrey Vyacheslavovich Vasilyev Timofei Evgenevich Grigoriev Yuriy Dmitrievich Zagoskin Sergei Nicolaevich Chvalun Sergey Ivanovich Kutsev Dmitry Vadimovich Goldshtein |
| author_facet | Tatiana Borisovna Bukharova Irina Alekseevna Nedorubova Viktoria Olegovna Mokrousova Anastasiia Yurevna Meglei Viktoriia Pavlovna Basina Andrey Anatolevich Nedorubov Andrey Vyacheslavovich Vasilyev Timofei Evgenevich Grigoriev Yuriy Dmitrievich Zagoskin Sergei Nicolaevich Chvalun Sergey Ivanovich Kutsev Dmitry Vadimovich Goldshtein |
| author_sort | Tatiana Borisovna Bukharova |
| collection | DOAJ |
| description | 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 <i>BMP2</i> 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 <i>BMP2</i> 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 <i>BMP2</i> gene has proven to be a more effective approach than the in vivo delivery of gene constructs for bone regeneration. |
| first_indexed | 2024-03-11T01:45:42Z |
| format | Article |
| id | doaj.art-fec95b186f1b45d78801e614ec12362c |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T01:45:42Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-fec95b186f1b45d78801e614ec12362c2023-11-18T16:19:41ZengMDPI AGCells2073-44092023-07-011213176210.3390/cells12131762Adenovirus-Based Gene Therapy for Bone Regeneration: A Comparative Analysis of In Vivo and Ex Vivo <i>BMP2</i> Gene DeliveryTatiana Borisovna Bukharova0Irina Alekseevna Nedorubova1Viktoria Olegovna Mokrousova2Anastasiia Yurevna Meglei3Viktoriia Pavlovna Basina4Andrey Anatolevich Nedorubov5Andrey Vyacheslavovich Vasilyev6Timofei Evgenevich Grigoriev7Yuriy Dmitrievich Zagoskin8Sergei Nicolaevich Chvalun9Sergey Ivanovich Kutsev10Dmitry Vadimovich Goldshtein11Research Centre for Medical Genetics, 115478 Moscow, RussiaResearch Centre for Medical Genetics, 115478 Moscow, RussiaResearch Centre for Medical Genetics, 115478 Moscow, RussiaResearch Centre for Medical Genetics, 115478 Moscow, RussiaResearch Centre for Medical Genetics, 115478 Moscow, RussiaInstitute 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, RussiaResearch Centre for Medical Genetics, 115478 Moscow, RussiaNRC “Kurchatov Institute”, 123182 Moscow, RussiaNRC “Kurchatov Institute”, 123182 Moscow, RussiaNRC “Kurchatov Institute”, 123182 Moscow, RussiaResearch Centre for Medical Genetics, 115478 Moscow, RussiaResearch Centre for Medical Genetics, 115478 Moscow, RussiaAdenovirus-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 <i>BMP2</i> 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 <i>BMP2</i> 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 <i>BMP2</i> gene has proven to be a more effective approach than the in vivo delivery of gene constructs for bone regeneration.https://www.mdpi.com/2073-4409/12/13/1762gene therapyadenoviral transductionmesenchymal stem cellspolylactide granulesplatelet rich plasmabone regeneration |
| spellingShingle | Tatiana Borisovna Bukharova Irina Alekseevna Nedorubova Viktoria Olegovna Mokrousova Anastasiia Yurevna Meglei Viktoriia Pavlovna Basina Andrey Anatolevich Nedorubov Andrey Vyacheslavovich Vasilyev Timofei Evgenevich Grigoriev Yuriy Dmitrievich Zagoskin Sergei Nicolaevich Chvalun Sergey Ivanovich Kutsev Dmitry Vadimovich Goldshtein Adenovirus-Based Gene Therapy for Bone Regeneration: A Comparative Analysis of In Vivo and Ex Vivo <i>BMP2</i> Gene Delivery Cells gene therapy adenoviral transduction mesenchymal stem cells polylactide granules platelet rich plasma bone regeneration |
| title | Adenovirus-Based Gene Therapy for Bone Regeneration: A Comparative Analysis of In Vivo and Ex Vivo <i>BMP2</i> Gene Delivery |
| title_full | Adenovirus-Based Gene Therapy for Bone Regeneration: A Comparative Analysis of In Vivo and Ex Vivo <i>BMP2</i> Gene Delivery |
| title_fullStr | Adenovirus-Based Gene Therapy for Bone Regeneration: A Comparative Analysis of In Vivo and Ex Vivo <i>BMP2</i> Gene Delivery |
| title_full_unstemmed | Adenovirus-Based Gene Therapy for Bone Regeneration: A Comparative Analysis of In Vivo and Ex Vivo <i>BMP2</i> Gene Delivery |
| title_short | Adenovirus-Based Gene Therapy for Bone Regeneration: A Comparative Analysis of In Vivo and Ex Vivo <i>BMP2</i> Gene Delivery |
| title_sort | adenovirus based gene therapy for bone regeneration a comparative analysis of in vivo and ex vivo i bmp2 i gene delivery |
| topic | gene therapy adenoviral transduction mesenchymal stem cells polylactide granules platelet rich plasma bone regeneration |
| url | https://www.mdpi.com/2073-4409/12/13/1762 |
| work_keys_str_mv | AT tatianaborisovnabukharova adenovirusbasedgenetherapyforboneregenerationacomparativeanalysisofinvivoandexvivoibmp2igenedelivery AT irinaalekseevnanedorubova adenovirusbasedgenetherapyforboneregenerationacomparativeanalysisofinvivoandexvivoibmp2igenedelivery AT viktoriaolegovnamokrousova adenovirusbasedgenetherapyforboneregenerationacomparativeanalysisofinvivoandexvivoibmp2igenedelivery AT anastasiiayurevnameglei adenovirusbasedgenetherapyforboneregenerationacomparativeanalysisofinvivoandexvivoibmp2igenedelivery AT viktoriiapavlovnabasina adenovirusbasedgenetherapyforboneregenerationacomparativeanalysisofinvivoandexvivoibmp2igenedelivery AT andreyanatolevichnedorubov adenovirusbasedgenetherapyforboneregenerationacomparativeanalysisofinvivoandexvivoibmp2igenedelivery AT andreyvyacheslavovichvasilyev adenovirusbasedgenetherapyforboneregenerationacomparativeanalysisofinvivoandexvivoibmp2igenedelivery AT timofeievgenevichgrigoriev adenovirusbasedgenetherapyforboneregenerationacomparativeanalysisofinvivoandexvivoibmp2igenedelivery AT yuriydmitrievichzagoskin adenovirusbasedgenetherapyforboneregenerationacomparativeanalysisofinvivoandexvivoibmp2igenedelivery AT sergeinicolaevichchvalun adenovirusbasedgenetherapyforboneregenerationacomparativeanalysisofinvivoandexvivoibmp2igenedelivery AT sergeyivanovichkutsev adenovirusbasedgenetherapyforboneregenerationacomparativeanalysisofinvivoandexvivoibmp2igenedelivery AT dmitryvadimovichgoldshtein adenovirusbasedgenetherapyforboneregenerationacomparativeanalysisofinvivoandexvivoibmp2igenedelivery |