Safety Study of an Original Mesenchymal Stromal Cell Secretome-Based Medicinal Product for Spermatogenesis Restoration
SCIENTIFIC RELEVANCE. Currently, there are no effective and safe medicinal products for idiopathic male infertility. Previous studies in two animal models of infertility (short-term cryptorchidism in rats and doxorubicin-induced testicular injury in mice) have shown the effectiveness of an originato...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | Russian |
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Ministry of Health of the Russian Federation, Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products»
2024-04-01
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| Series: | Безопасность и риск фармакотерапии |
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| Online Access: | https://www.risksafety.ru/jour/article/view/364 |
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| author | A. O. Monakova G. D. Sagaradze V. Yu. Balabanyan N. A. Basalova A. A. Matichina A. A. Matichin K. L. Kryshen V. S. Popov Zh. A. Akopyan A. Yu. Efimenko |
| author_facet | A. O. Monakova G. D. Sagaradze V. Yu. Balabanyan N. A. Basalova A. A. Matichina A. A. Matichin K. L. Kryshen V. S. Popov Zh. A. Akopyan A. Yu. Efimenko |
| author_sort | A. O. Monakova |
| collection | DOAJ |
| description | SCIENTIFIC RELEVANCE. Currently, there are no effective and safe medicinal products for idiopathic male infertility. Previous studies in two animal models of infertility (short-term cryptorchidism in rats and doxorubicin-induced testicular injury in mice) have shown the effectiveness of an originator medicinal product based on the mesenchymal stromal cell (MSC) secretome.AIM. The aim of the study was to evaluate the toxicity profile of the MSC secretome-based medicinal product in rats after local intratesticular or intramuscular administration.MATERIALS AND METHODS. The MSC secretome is a combination of factors secreted by MSCs in low-glucose Dulbecco’s modified Eagle’s medium (DMEM-LG) for MSC conditioning. In the single-dose toxicity study, the MSC secretome-based medicinal product was injected under the testicular tunica albuginea of male Wistar rats (15 per group) at doses of 15 and 25 relative units (RU) per animal, which are 1.5 and 2.5 times higher than the therapeutic dose (10 RU). In the repeat-dose toxicity study, male Wistar rats (10 per group) received intramuscular thigh injections of the medicinal product on days 1, 6, and 12 at doses of 15 and 25 RU per animal. The local tolerance study involved histopathological examination of the testes and thighs at the injection site. All studies included control groups of intact animals and animals similarly injected with blank DMEM-LG. The early follow-up period was 14 days, and the late follow-up period was 42 days.RESULTS. The rats showed no changes in the general condition after single and repeated doses of the MSC secretome-based medicinal product. Single subtunical doses induced moderate irritation; its signs included pathological changes in individual seminiferous tubules: epithelial atrophy (70% of the animals on day 14; 55% at late follow-up) and sperm stasis (70% of the animals). Similar changes were observed in the blank DMEM-LG group (up to 80% of the animals). There were no pathological changes in the tissues after repeated injections. A transient increase in alkaline phosphatase activity was detected in animals after their third intramuscular injection at a dose of 25 RU; the other biochemical parameters were normal in all study groups.CONCLUSIONS. The MSC secretome-based medicinal product has a favourable safety profile following both intratesticular and intramuscular administration, as it does not cause any permanent changes in the studied organs and tissues. |
| first_indexed | 2024-03-08T22:26:40Z |
| format | Article |
| id | doaj.art-b94ca0f8e8744b01bc7e6f70d496c846 |
| institution | Directory Open Access Journal |
| issn | 2312-7821 2619-1164 |
| language | Russian |
| last_indexed | 2024-04-24T13:55:01Z |
| publishDate | 2024-04-01 |
| publisher | Ministry of Health of the Russian Federation, Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» |
| record_format | Article |
| series | Безопасность и риск фармакотерапии |
| spelling | doaj.art-b94ca0f8e8744b01bc7e6f70d496c8462024-04-03T17:56:38ZrusMinistry of Health of the Russian Federation, Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products»Безопасность и риск фармакотерапии2312-78212619-11642024-04-011219911610.30895/2312-7821-2023-364310Safety Study of an Original Mesenchymal Stromal Cell Secretome-Based Medicinal Product for Spermatogenesis RestorationA. O. Monakova0G. D. Sagaradze1V. Yu. Balabanyan2N. A. Basalova3A. A. Matichina4A. A. Matichin5K. L. Kryshen6V. S. Popov7Zh. A. Akopyan8A. Yu. Efimenko9Institute for Regenerative Medicine, Lomonosov Moscow State University Medical Research and Educational Center; Faculty of Medicine, Lomonosov Moscow State UniversityInstitute for Regenerative Medicine, Lomonosov Moscow State University Medical Research and Educational CenterInstitute for Regenerative Medicine, Lomonosov Moscow State University Medical Research and Educational Center; Faculty of Medicine, Lomonosov Moscow State UniversityInstitute for Regenerative Medicine, Lomonosov Moscow State University Medical Research and Educational Center; Faculty of Medicine, Lomonosov Moscow State UniversityResearch-and-manufacturing company “HOME OF PHARMACY”Research-and-manufacturing company “HOME OF PHARMACY”Research-and-manufacturing company “HOME OF PHARMACY”Institute for Regenerative Medicine, Lomonosov Moscow State University Medical Research and Educational Center; Faculty of Medicine, Lomonosov Moscow State UniversityInstitute for Regenerative Medicine, Lomonosov Moscow State University Medical Research and Educational Center; Faculty of Medicine, Lomonosov Moscow State UniversityInstitute for Regenerative Medicine, Lomonosov Moscow State University Medical Research and Educational Center; Faculty of Medicine, Lomonosov Moscow State UniversitySCIENTIFIC RELEVANCE. Currently, there are no effective and safe medicinal products for idiopathic male infertility. Previous studies in two animal models of infertility (short-term cryptorchidism in rats and doxorubicin-induced testicular injury in mice) have shown the effectiveness of an originator medicinal product based on the mesenchymal stromal cell (MSC) secretome.AIM. The aim of the study was to evaluate the toxicity profile of the MSC secretome-based medicinal product in rats after local intratesticular or intramuscular administration.MATERIALS AND METHODS. The MSC secretome is a combination of factors secreted by MSCs in low-glucose Dulbecco’s modified Eagle’s medium (DMEM-LG) for MSC conditioning. In the single-dose toxicity study, the MSC secretome-based medicinal product was injected under the testicular tunica albuginea of male Wistar rats (15 per group) at doses of 15 and 25 relative units (RU) per animal, which are 1.5 and 2.5 times higher than the therapeutic dose (10 RU). In the repeat-dose toxicity study, male Wistar rats (10 per group) received intramuscular thigh injections of the medicinal product on days 1, 6, and 12 at doses of 15 and 25 RU per animal. The local tolerance study involved histopathological examination of the testes and thighs at the injection site. All studies included control groups of intact animals and animals similarly injected with blank DMEM-LG. The early follow-up period was 14 days, and the late follow-up period was 42 days.RESULTS. The rats showed no changes in the general condition after single and repeated doses of the MSC secretome-based medicinal product. Single subtunical doses induced moderate irritation; its signs included pathological changes in individual seminiferous tubules: epithelial atrophy (70% of the animals on day 14; 55% at late follow-up) and sperm stasis (70% of the animals). Similar changes were observed in the blank DMEM-LG group (up to 80% of the animals). There were no pathological changes in the tissues after repeated injections. A transient increase in alkaline phosphatase activity was detected in animals after their third intramuscular injection at a dose of 25 RU; the other biochemical parameters were normal in all study groups.CONCLUSIONS. The MSC secretome-based medicinal product has a favourable safety profile following both intratesticular and intramuscular administration, as it does not cause any permanent changes in the studied organs and tissues.https://www.risksafety.ru/jour/article/view/364mesenchymal stromal cellsmesenchymal stromal cell secretomespermatogenesisrodentssafetygeneral toxicitysubchronic toxicitylocal toxicity |
| spellingShingle | A. O. Monakova G. D. Sagaradze V. Yu. Balabanyan N. A. Basalova A. A. Matichina A. A. Matichin K. L. Kryshen V. S. Popov Zh. A. Akopyan A. Yu. Efimenko Safety Study of an Original Mesenchymal Stromal Cell Secretome-Based Medicinal Product for Spermatogenesis Restoration Безопасность и риск фармакотерапии mesenchymal stromal cells mesenchymal stromal cell secretome spermatogenesis rodents safety general toxicity subchronic toxicity local toxicity |
| title | Safety Study of an Original Mesenchymal Stromal Cell Secretome-Based Medicinal Product for Spermatogenesis Restoration |
| title_full | Safety Study of an Original Mesenchymal Stromal Cell Secretome-Based Medicinal Product for Spermatogenesis Restoration |
| title_fullStr | Safety Study of an Original Mesenchymal Stromal Cell Secretome-Based Medicinal Product for Spermatogenesis Restoration |
| title_full_unstemmed | Safety Study of an Original Mesenchymal Stromal Cell Secretome-Based Medicinal Product for Spermatogenesis Restoration |
| title_short | Safety Study of an Original Mesenchymal Stromal Cell Secretome-Based Medicinal Product for Spermatogenesis Restoration |
| title_sort | safety study of an original mesenchymal stromal cell secretome based medicinal product for spermatogenesis restoration |
| topic | mesenchymal stromal cells mesenchymal stromal cell secretome spermatogenesis rodents safety general toxicity subchronic toxicity local toxicity |
| url | https://www.risksafety.ru/jour/article/view/364 |
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