Vocal fold restoration after scarring: biocompatibility and efficacy of an MSC-based bioequivalent
Abstract Background There is growing interest to application of regenerative medicine approaches in otorhinolaryngological practice, especially in the framework of the therapy of vocal fold (VF) scar lesions. The used conservative and surgical methods, despite the achieved positive outcomes, are fre...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-10-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-023-03534-x |
| _version_ | 1827635342764670976 |
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| author | Mikhail Svistushkin Anastasia Shpichka Polina Bikmulina Alexey Fayzullin Anna Zolotova Nastasia Kosheleva Liliya Selezneva Boris Shavkuta Viktoria Lobacheva Anna Nikiforova Peter Kochetkov Svetlana Kotova Svetlana Starostina Anatoly Shekhter Andrey Svistunov Valeriy Svistushkin Peter Timashev |
| author_facet | Mikhail Svistushkin Anastasia Shpichka Polina Bikmulina Alexey Fayzullin Anna Zolotova Nastasia Kosheleva Liliya Selezneva Boris Shavkuta Viktoria Lobacheva Anna Nikiforova Peter Kochetkov Svetlana Kotova Svetlana Starostina Anatoly Shekhter Andrey Svistunov Valeriy Svistushkin Peter Timashev |
| author_sort | Mikhail Svistushkin |
| collection | DOAJ |
| description | Abstract Background There is growing interest to application of regenerative medicine approaches in otorhinolaryngological practice, especially in the framework of the therapy of vocal fold (VF) scar lesions. The used conservative and surgical methods, despite the achieved positive outcomes, are frequently unpredictable and do not result in the restoration of the VF’s lamina propria’s structure, which provides the mechanical properties necessary for vibration. In this connection, the aim of this study was to ascertain the safety and efficacy of a bioequivalent in the treatment of VF scars using a rabbit model of chronic damage. Methods The bioequivalent consisted of a hydrogel system based on a PEG-fibrin conjugate and human bone marrow-derived MSC. It was characterized and implanted heterotopically into rats and orthotopically into rabbits after VF scar excision. Results We showed that the fabricated bioequivalent consisted of viable cells retaining their metabolic and proliferative activity. While being implanted heterotopically, it had induced the low inflammatory reaction in 7 days and was well tolerated. The orthotopic implantation showed that the gel application was characterized by a lower hemorrhage intensity (p = 0.03945). The intensity of stridor and respiratory rate between the groups in total and between separate groups had no statistically significant difference (p = 0.96 and p = 1; p = 0.9593 and p = 0.97…1, respectively). In 3 days post-implantation, MSC were detected only in the tissues closely surrounding the VF defect. The bioequivalent injection caused that the scar collagen fibers were packed looser and more frequently mutually parallel that is inherent in the native tissue (p = 0.018). In all experimental groups, the fibrous tissue’s ingrowth in the adjacent exterior muscle tissue was observed; however, in Group 4 (PEG-Fibrin + MSC), it was much less pronounced than it was in Group 1 (normal saline) (p = 0.008). The difference between the thicknesses of the lamina propria in the control group and in Group 4 was not revealed to be statistically significant (p = 0.995). The Young’s modulus of the VF after the bioequivalent implantation (1.15 ± 0.25 kPa) did not statistically significantly differ from the intact VF modulus (1.17 ± 0.45 kPa); therefore, the tissue properties in this group more closely resembled the intact VF. Conclusions The developed bioequivalent showed to be biocompatible and highly efficient in the restoration of VF’s tissue. |
| first_indexed | 2024-03-09T15:26:26Z |
| format | Article |
| id | doaj.art-8e6f589df9574642845eea2ac6a1324c |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-03-09T15:26:26Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-8e6f589df9574642845eea2ac6a1324c2023-11-26T12:31:01ZengBMCStem Cell Research & Therapy1757-65122023-10-0114111910.1186/s13287-023-03534-xVocal fold restoration after scarring: biocompatibility and efficacy of an MSC-based bioequivalentMikhail Svistushkin0Anastasia Shpichka1Polina Bikmulina2Alexey Fayzullin3Anna Zolotova4Nastasia Kosheleva5Liliya Selezneva6Boris Shavkuta7Viktoria Lobacheva8Anna Nikiforova9Peter Kochetkov10Svetlana Kotova11Svetlana Starostina12Anatoly Shekhter13Andrey Svistunov14Valeriy Svistushkin15Peter Timashev16Department for ENT Diseases, Sechenov UniversityInstitute for Regenerative Medicine, Sechenov UniversityInstitute for Regenerative Medicine, Sechenov UniversityInstitute for Regenerative Medicine, Sechenov UniversityDepartment for ENT Diseases, Sechenov UniversityInstitute for Regenerative Medicine, Sechenov UniversityDepartment for ENT Diseases, Sechenov UniversityInstitute for Regenerative Medicine, Sechenov UniversityDepartment for ENT Diseases, Sechenov UniversityDepartment for ENT Diseases, Sechenov UniversityDepartment for ENT Diseases, Sechenov UniversityInstitute for Regenerative Medicine, Sechenov UniversityDepartment for ENT Diseases, Sechenov UniversityInstitute for Regenerative Medicine, Sechenov UniversitySechenov UniversityDepartment for ENT Diseases, Sechenov UniversityInstitute for Regenerative Medicine, Sechenov UniversityAbstract Background There is growing interest to application of regenerative medicine approaches in otorhinolaryngological practice, especially in the framework of the therapy of vocal fold (VF) scar lesions. The used conservative and surgical methods, despite the achieved positive outcomes, are frequently unpredictable and do not result in the restoration of the VF’s lamina propria’s structure, which provides the mechanical properties necessary for vibration. In this connection, the aim of this study was to ascertain the safety and efficacy of a bioequivalent in the treatment of VF scars using a rabbit model of chronic damage. Methods The bioequivalent consisted of a hydrogel system based on a PEG-fibrin conjugate and human bone marrow-derived MSC. It was characterized and implanted heterotopically into rats and orthotopically into rabbits after VF scar excision. Results We showed that the fabricated bioequivalent consisted of viable cells retaining their metabolic and proliferative activity. While being implanted heterotopically, it had induced the low inflammatory reaction in 7 days and was well tolerated. The orthotopic implantation showed that the gel application was characterized by a lower hemorrhage intensity (p = 0.03945). The intensity of stridor and respiratory rate between the groups in total and between separate groups had no statistically significant difference (p = 0.96 and p = 1; p = 0.9593 and p = 0.97…1, respectively). In 3 days post-implantation, MSC were detected only in the tissues closely surrounding the VF defect. The bioequivalent injection caused that the scar collagen fibers were packed looser and more frequently mutually parallel that is inherent in the native tissue (p = 0.018). In all experimental groups, the fibrous tissue’s ingrowth in the adjacent exterior muscle tissue was observed; however, in Group 4 (PEG-Fibrin + MSC), it was much less pronounced than it was in Group 1 (normal saline) (p = 0.008). The difference between the thicknesses of the lamina propria in the control group and in Group 4 was not revealed to be statistically significant (p = 0.995). The Young’s modulus of the VF after the bioequivalent implantation (1.15 ± 0.25 kPa) did not statistically significantly differ from the intact VF modulus (1.17 ± 0.45 kPa); therefore, the tissue properties in this group more closely resembled the intact VF. Conclusions The developed bioequivalent showed to be biocompatible and highly efficient in the restoration of VF’s tissue.https://doi.org/10.1186/s13287-023-03534-xVocal foldsMesenchymal stromal cellsFibrinTissue engineeringRegenerative medicineScarring |
| spellingShingle | Mikhail Svistushkin Anastasia Shpichka Polina Bikmulina Alexey Fayzullin Anna Zolotova Nastasia Kosheleva Liliya Selezneva Boris Shavkuta Viktoria Lobacheva Anna Nikiforova Peter Kochetkov Svetlana Kotova Svetlana Starostina Anatoly Shekhter Andrey Svistunov Valeriy Svistushkin Peter Timashev Vocal fold restoration after scarring: biocompatibility and efficacy of an MSC-based bioequivalent Stem Cell Research & Therapy Vocal folds Mesenchymal stromal cells Fibrin Tissue engineering Regenerative medicine Scarring |
| title | Vocal fold restoration after scarring: biocompatibility and efficacy of an MSC-based bioequivalent |
| title_full | Vocal fold restoration after scarring: biocompatibility and efficacy of an MSC-based bioequivalent |
| title_fullStr | Vocal fold restoration after scarring: biocompatibility and efficacy of an MSC-based bioequivalent |
| title_full_unstemmed | Vocal fold restoration after scarring: biocompatibility and efficacy of an MSC-based bioequivalent |
| title_short | Vocal fold restoration after scarring: biocompatibility and efficacy of an MSC-based bioequivalent |
| title_sort | vocal fold restoration after scarring biocompatibility and efficacy of an msc based bioequivalent |
| topic | Vocal folds Mesenchymal stromal cells Fibrin Tissue engineering Regenerative medicine Scarring |
| url | https://doi.org/10.1186/s13287-023-03534-x |
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