Novel Molecular Vehicle-Based Approach for Cardiac Cell Transplantation Leads to Rapid Electromechanical Graft–Host Coupling
Myocardial remodeling is an inevitable risk factor for cardiac arrhythmias and can potentially be corrected with cell therapy. Although the generation of cardiac cells ex vivo is possible, specific approaches to cell replacement therapy remain unclear. On the one hand, adhesive myocyte cells must be...
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/12/10406 |
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| author | Aleria Aitova Serafima Scherbina Andrey Berezhnoy Mikhail Slotvitsky Valeriya Tsvelaya Tatyana Sergeeva Elena Turchaninova Elizaveta Rybkina Sergey Bakumenko Ilya Sidorov Mikhail A. Popov Vladislav Dontsov Evgeniy G. Agafonov Anton E. Efimov Igor Agapov Dmitriy Zybin Dmitriy Shumakov Konstantin Agladze |
| author_facet | Aleria Aitova Serafima Scherbina Andrey Berezhnoy Mikhail Slotvitsky Valeriya Tsvelaya Tatyana Sergeeva Elena Turchaninova Elizaveta Rybkina Sergey Bakumenko Ilya Sidorov Mikhail A. Popov Vladislav Dontsov Evgeniy G. Agafonov Anton E. Efimov Igor Agapov Dmitriy Zybin Dmitriy Shumakov Konstantin Agladze |
| author_sort | Aleria Aitova |
| collection | DOAJ |
| description | Myocardial remodeling is an inevitable risk factor for cardiac arrhythmias and can potentially be corrected with cell therapy. Although the generation of cardiac cells ex vivo is possible, specific approaches to cell replacement therapy remain unclear. On the one hand, adhesive myocyte cells must be viable and conjugated with the electromechanical syncytium of the recipient tissue, which is unattainable without an external scaffold substrate. On the other hand, the outer scaffold may hinder cell delivery, for example, making intramyocardial injection difficult. To resolve this contradiction, we developed molecular vehicles that combine a wrapped (rather than outer) polymer scaffold that is enveloped by the cell and provides excitability restoration (lost when cells were harvested) before engraftment. It also provides a coating with human fibronectin, which initiates the process of graft adhesion into the recipient tissue and can carry fluorescent markers for the external control of the non-invasive cell position. In this work, we used a type of scaffold that allowed us to use the advantages of a scaffold-free cell suspension for cell delivery. Fragmented nanofibers (0.85 µm ± 0.18 µm in diameter) with fluorescent labels were used, with solitary cells seeded on them. Cell implantation experiments were performed in vivo. The proposed molecular vehicles made it possible to establish rapid (30 min) electromechanical contact between excitable grafts and the recipient heart. Excitable grafts were visualized with optical mapping on a rat heart with Langendorff perfusion at a 0.72 ± 0.32 Hz heart rate. Thus, the pre-restored grafts’ excitability (with the help of a wrapped polymer scaffold) allowed rapid electromechanical coupling with the recipient tissue. This information could provide a basis for the reduction of engraftment arrhythmias in the first days after cell therapy. |
| first_indexed | 2024-03-11T02:20:33Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T02:20:33Z |
| publishDate | 2023-06-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-96e289df9f5f45e6bf8bd428df7566ca2023-11-18T10:53:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124121040610.3390/ijms241210406Novel Molecular Vehicle-Based Approach for Cardiac Cell Transplantation Leads to Rapid Electromechanical Graft–Host CouplingAleria Aitova0Serafima Scherbina1Andrey Berezhnoy2Mikhail Slotvitsky3Valeriya Tsvelaya4Tatyana Sergeeva5Elena Turchaninova6Elizaveta Rybkina7Sergey Bakumenko8Ilya Sidorov9Mikhail A. Popov10Vladislav Dontsov11Evgeniy G. Agafonov12Anton E. Efimov13Igor Agapov14Dmitriy Zybin15Dmitriy Shumakov16Konstantin Agladze17Laboratory of Experimental and Cellular Medicine, Moscow Institute of Physics and Technology, Institutskiy Lane 9, 141700 Dolgoprudny, RussiaLaboratory of Experimental and Cellular Medicine, Moscow Institute of Physics and Technology, Institutskiy Lane 9, 141700 Dolgoprudny, RussiaLaboratory of Experimental and Cellular Medicine, Moscow Institute of Physics and Technology, Institutskiy Lane 9, 141700 Dolgoprudny, RussiaLaboratory of Experimental and Cellular Medicine, Moscow Institute of Physics and Technology, Institutskiy Lane 9, 141700 Dolgoprudny, RussiaLaboratory of Experimental and Cellular Medicine, Moscow Institute of Physics and Technology, Institutskiy Lane 9, 141700 Dolgoprudny, RussiaLaboratory of Experimental and Cellular Medicine, Moscow Institute of Physics and Technology, Institutskiy Lane 9, 141700 Dolgoprudny, RussiaLaboratory of Experimental and Cellular Medicine, Moscow Institute of Physics and Technology, Institutskiy Lane 9, 141700 Dolgoprudny, RussiaLaboratory of Experimental and Cellular Medicine, Moscow Institute of Physics and Technology, Institutskiy Lane 9, 141700 Dolgoprudny, RussiaLaboratory of Experimental and Cellular Medicine, Moscow Institute of Physics and Technology, Institutskiy Lane 9, 141700 Dolgoprudny, RussiaNanobiomedicine Division, Sirius University of Science and Technology, 1 Olympic Ave, 354340 Sochi, RussiaM.F. Vladimirsky Moscow Regional Clinical Research Institute, Schepkina St. 61/2, 129110 Moscow, RussiaM.F. Vladimirsky Moscow Regional Clinical Research Institute, Schepkina St. 61/2, 129110 Moscow, RussiaM.F. Vladimirsky Moscow Regional Clinical Research Institute, Schepkina St. 61/2, 129110 Moscow, RussiaAcademician V.I. Shumakov National Medical Research Center of Transplantology and Artificial Organs, Ministry of Health of the Russian Federation, 1 Schukinskaya St., 123182 Moscow, RussiaAcademician V.I. Shumakov National Medical Research Center of Transplantology and Artificial Organs, Ministry of Health of the Russian Federation, 1 Schukinskaya St., 123182 Moscow, RussiaM.F. Vladimirsky Moscow Regional Clinical Research Institute, Schepkina St. 61/2, 129110 Moscow, RussiaM.F. Vladimirsky Moscow Regional Clinical Research Institute, Schepkina St. 61/2, 129110 Moscow, RussiaLaboratory of Experimental and Cellular Medicine, Moscow Institute of Physics and Technology, Institutskiy Lane 9, 141700 Dolgoprudny, RussiaMyocardial remodeling is an inevitable risk factor for cardiac arrhythmias and can potentially be corrected with cell therapy. Although the generation of cardiac cells ex vivo is possible, specific approaches to cell replacement therapy remain unclear. On the one hand, adhesive myocyte cells must be viable and conjugated with the electromechanical syncytium of the recipient tissue, which is unattainable without an external scaffold substrate. On the other hand, the outer scaffold may hinder cell delivery, for example, making intramyocardial injection difficult. To resolve this contradiction, we developed molecular vehicles that combine a wrapped (rather than outer) polymer scaffold that is enveloped by the cell and provides excitability restoration (lost when cells were harvested) before engraftment. It also provides a coating with human fibronectin, which initiates the process of graft adhesion into the recipient tissue and can carry fluorescent markers for the external control of the non-invasive cell position. In this work, we used a type of scaffold that allowed us to use the advantages of a scaffold-free cell suspension for cell delivery. Fragmented nanofibers (0.85 µm ± 0.18 µm in diameter) with fluorescent labels were used, with solitary cells seeded on them. Cell implantation experiments were performed in vivo. The proposed molecular vehicles made it possible to establish rapid (30 min) electromechanical contact between excitable grafts and the recipient heart. Excitable grafts were visualized with optical mapping on a rat heart with Langendorff perfusion at a 0.72 ± 0.32 Hz heart rate. Thus, the pre-restored grafts’ excitability (with the help of a wrapped polymer scaffold) allowed rapid electromechanical coupling with the recipient tissue. This information could provide a basis for the reduction of engraftment arrhythmias in the first days after cell therapy.https://www.mdpi.com/1422-0067/24/12/10406cardiovascularcell culturingelectrophysiological couplingelectrospinningengraftmentmicrocarriers |
| spellingShingle | Aleria Aitova Serafima Scherbina Andrey Berezhnoy Mikhail Slotvitsky Valeriya Tsvelaya Tatyana Sergeeva Elena Turchaninova Elizaveta Rybkina Sergey Bakumenko Ilya Sidorov Mikhail A. Popov Vladislav Dontsov Evgeniy G. Agafonov Anton E. Efimov Igor Agapov Dmitriy Zybin Dmitriy Shumakov Konstantin Agladze Novel Molecular Vehicle-Based Approach for Cardiac Cell Transplantation Leads to Rapid Electromechanical Graft–Host Coupling International Journal of Molecular Sciences cardiovascular cell culturing electrophysiological coupling electrospinning engraftment microcarriers |
| title | Novel Molecular Vehicle-Based Approach for Cardiac Cell Transplantation Leads to Rapid Electromechanical Graft–Host Coupling |
| title_full | Novel Molecular Vehicle-Based Approach for Cardiac Cell Transplantation Leads to Rapid Electromechanical Graft–Host Coupling |
| title_fullStr | Novel Molecular Vehicle-Based Approach for Cardiac Cell Transplantation Leads to Rapid Electromechanical Graft–Host Coupling |
| title_full_unstemmed | Novel Molecular Vehicle-Based Approach for Cardiac Cell Transplantation Leads to Rapid Electromechanical Graft–Host Coupling |
| title_short | Novel Molecular Vehicle-Based Approach for Cardiac Cell Transplantation Leads to Rapid Electromechanical Graft–Host Coupling |
| title_sort | novel molecular vehicle based approach for cardiac cell transplantation leads to rapid electromechanical graft host coupling |
| topic | cardiovascular cell culturing electrophysiological coupling electrospinning engraftment microcarriers |
| url | https://www.mdpi.com/1422-0067/24/12/10406 |
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