Issue 25-2, 2026

Original article

Assessment of the Pro-Regenerative Activity of the Altai Maral Antler Mesenchymal Stromal Cell Secretome: Experimental Study Results



ORCIDPetr S. Eremin, ORCIDPavel A. Markov*

National Medical Research Center for Rehabilitation and Balneology, Moscow, Russia


ABSTRACT

INTRODUCTION.  It is known that the secretome of mesenchymal stromal cells exhibits high efficacy in the therapy of various diseases. However, there are limitations hindering its widespread introduction into clinical practice, such as donor variability including donor age, health status, and genetic characteristics. In this regard, the search for new approaches and methods to address this issue is ongoing. A unique natural resource is the antlers of the Altai maral, which represent a natural “bioreactor” of stem cells and growth factors. Despite the increasing interest in this subject, to date there are no studies evaluating the pro-regenerative effect of the secretome from Altai maral antler mesenchymal stromal cells.

AIM.  To characterize the component composition and biological activity of the stem cell secretome from Altai maral antlers to scientifically substantiate the possibility of its use as a basis for the development of cell-free therapeutic products in regenerative medicine.

MATERIALS AND METHODS.  The study was conducted at the National Medical Research Center for Rehabilitation and Balneology of the Ministry of Health of Russia, from October to December 2025. Concentration of the secretome from Altai maral antler mesenchymal stromal cells (MSC-MA) and human adipose tissue mesenchymal stromal cells (MSC-AT) was performed by lyophilization. The pro-regenerative effect of the MSC-MA and MSC-AT secretomes was evaluated using a model of acid-induced damage to human fibroblasts. Using light and luminescence microscopy, as well as flow cytometry, the morphology, proliferative activity, and the number of live, apoptotic, and dead cells in the human fibroblast population were assessed.

RESULTS.  It was established that the concentration of growth factors in the MSC-MA secretome is on average 50 % higher compared to MSC-AT. The ability of MSC-MA to stimulate the viability of fibroblasts with acid-induced damage was revealed, which is expressed in the restoration of their proliferative activity, an increase in the number of live cells in the population from 48 ± 7 % to 85 ± 3 %, and a decrease in the number of apoptotic cells from 24 ± 4 % to 5 ± 1 %. It was shown that the effectiveness of the stimulating effect of the MSC-MA secretome is comparable to the pro-regenerative effect of the human MSC-AT secretome.

DISCUSSION.  The obtained results complement the literature data and demonstrate that the MSC-MA secretome, which is xenogeneic with respect to human fibroblasts, is capable of exerting a pro-regenerative effect and stimulating the recovery of the fibroblast cell population with acid-induced damage.

CONCLUSION.  The obtained results confirm the promising potential of using MSC-AS and MSC-AT as a biological resource for the development of cell-free therapeutic products, and also emphasize the need to select an optimal method for obtaining the secretome to maximally preserve its functional activity.


KEYWORDS: cellular secretome, stromal-vascular fraction of Altai maral antler, stromal-vascular fraction of human adipose tissue, fibroblasts, regeneration

FOR CITATION: Eremin P.S., Markov P.A. Assessment of the Pro-Regenerative Activity of the Altai Maral Antler Mesenchymal Stromal Cell Secretome: Experimental Study Results. Bulletin of Rehabilitation Medicine. 2026; 25(2):33–41. https://doi.org/10.38025/2078-1962-2026-25-2-33-41 (In Russ.).

FOR CORRESPONDENCE:

Pavel A. Markov, Е-mail:  markovpa@nmicrk.ru,  p.a.markov@mail.ru


References:

  1. Lu W., Allickson J. Mesenchymal stromal cell therapy: Progress to date and future outlook. Mol Ther. 2025; 33(6): 2679–2688. https://doi.org/10.1016/j.ymthe.2025.02.003
  2. Ma H., Siu W.S., Leung P.C. The Potential of MSC-Based Cell-Free Therapy in Wound Healing-A Thorough Literature Review. Int J Mol Sci. 2023; 24(11): 9356. https://doi.org/10.3390/ijms24119356
  3. Sohrabi B., Dayeri B., Zahedi E., et al. Mesenchymal stem cell (MSC)-derived exosomes as novel vehicles for delivery of miRNAs in cancer therapy. Cancer Gene Ther. 2022; 29(8–9): 1105–1116. https://doi.org/10.1038/s41417-022-00427-8
  4. Li X., Zhang D., Yu Y., Wang L., Zhao M. Umbilical cord-derived mesenchymal stem cell secretome promotes skin regeneration and rejuvenation: From mechanism to therapeutics. Cell Prolif. 2024; 57(4): e13586. https://doi.org/10.1111/cpr.13586
  5. Bar J.K., Lis-Nawara A., Grelewski P.G. Dental Pulp Stem Cell-Derived Secretome and Its Regenerative Potential. Int J Mol Sci. 2021; 22(21): 12018. https://doi.org/10.3390/ijms222112018
  6. Trzyna A., Banaś-Ząbczyk A. Adipose-Derived Stem Cells Secretome and Its Potential Application in “Stem Cell-Free Therapy”. Biomolecules. 2021; 11(6): 878. https://doi.org/10.3390/biom11060878
  7. Singh N., Choonara Y.E., Kumar P. Method standardization of secretome production, collection, and characterization: New insights and challenges. Regen Ther. 2025; 29: 466–473. https://doi.org/10.1016/j.reth.2025.04.005
  8. Zununi Vahed S., Hejazian S.M., Bakari W.N., et al. Milking mesenchymal stem cells: Updated protocols for cell lysate, secretome, and exosome extraction, and comparative analysis of their therapeutic potential. Methods. 2025; 238: 40–60. https://doi.org/10.1016/j.ymeth.2025.03.004
  9. Renecker L. Producing & Processing Reindeer Velvet Antler. 1994; 8.
  10. Khvorost O., Rudnyk A., Fedchenkova Y., et al. Prospects for expanding the range of medicinal products based on velvet antlers. Social Pharmacy in Health Care. 2025; 11: 80–92. https://doi.org/10.24959/sphhcj.25.347
  11. Смирнова И.Н., Суслов Н.И., Хлусов И.А. и др. Экспериментальное обоснование применения пантов марала на фоне экстремальных психоэмоциональных нагрузок. Биомедицина. 2019; 3: 33–40. https://doi.org/10.33647/2074-5982-15-3-33-40 [Smirnova I.N., Suslov N.I., Khlusov I.A., et al. Experimental substantiation of the use of maral deer antlers for combating extreme psycho-emotional stress. Journal Biomed. 2019; 3: 33–40. https://doi.org/10.33647/2074-5982-15-3-33-40 (In Russ.).]
  12. Лунин К.П., Турецкова В.Ф., Макарова О.Г. Изучение стабильности высушенной крови марала в условиях стресс-испытаний. Фармация. 2018; 67(4): 29–33. https://doi.org/10.29296/25419218-2018-04-06 [Lunin K.P., Turetskova V.F., Makarova O.G. Investigation of the stability of dried maral (cervus elaphus) blood during stress tests. Pharmacy. 2018; 67(4): 29–33. https://doi.org/10.29296/25419218-2018-04-06 (In Russ.).]
  13. Верещагина С.В., Смирнова И.Н., Абдулкина Н.Г., Баранкин Б.В. Эффективность использования оленьих рогов из бархатной скорлупы марала в коррекции нарушений иммунной системы у спортсменов. Современные вопросы биомедицины. 2021; 5(4): 1. https://doi.org/10.51871/2588-0500_2021_05_04_1 [Vereshchagina S.V., Smirnova I.N., Abdulkina N.G., Barankin B.V. The effectiveness of using maral velvet antlers in the correction of immune dysfunction in athletes. Modern Issues of Biomedicine. 2021; 5(4): 1. https://doi.org/10.51871/2588-0500_2021_05_04_1 (In Russ.).]
  14. Еремин П.С., Рожкова Е.А., Гильмутдинова И.Р. Возможности использования клеточного секретома для стимуляции регенерации мягких тканей: обзор. Вестник восстановительной медицины. 2025; 24(5): 106–112. https://doi.org/10.38025/2078-1962-2025-24-5-106-112 [Eremin P.S., Rozhkova E.A., Gilmutdinova I.R. Possibilities of Using Cellular Secretome to Stimulate Soft Tissue Regeneration: a Review. Bulletin of Rehabilitation Medicine. 2025; 24(5): 106–112. https://doi.org/10.38025/2078-1962-2025-24-5-106-112 (In Russ.).]
  15. Sendera A., Kubis H., Pałka A., Banaś-Ząbczyk A. Therapeutic and Clinical Potential of Adipose-Derived Stem Cell Secretome for Skin Regeneration. Cells. 2025; 14(21): 1727. https://doi.org/10.3390/cells14211727
  16. Bar J.K., Lis-Nawara A., Grelewski P.G. Dental Pulp Stem Cell-Derived Secretome and Its Regenerative Potential. Int J Mol Sci. 2021; 22(21): 12018. https://doi.org/10.3390/ijms222112018
  17. Donato L., Scimone C., Alibrandi S., et al. Human retinal secretome: A cross-link between mesenchymal and retinal cells. World J Stem Cells. 2023; 15(7): 665–686. https://doi.org/10.4252/wjsc.v15.i7.665
  18. Klaymook S., Tirawanchai N., Wichitwiengrat S., et al. MSC secretome from amniotic fluid halts IL-1β and TNF-α inflammation via the ERK/MAPK pathway, promoting cartilage regeneration in OA in vitro. J Stem Cells Regen Med. 2024; 20(1): 3–13. https://doi.org/10.46582/jsrm.2001002
  19. Jarquín-Yáñez K., Aguilar-Sandoval D.M., Piñón-Zárate G., et al. Growth Factor-Primed WJ-MSC Secretome Enhances Fibroblast Expansion In vitro. Biomedicines. 2025; 13(12): 2863. https://doi.org/10.3390/biomedicines13122863
  20. Михайлов Н.О., Глухов А.А., Андреев А.А. и др. Клинико-морфологические аспекты применения измельченных слайсов пантов марала в лечении асептических ран мягких тканей. Московский хирургический журнал. 2025; 1: 148–155. https://doi.org/10.17238/2072-3180-2025-1-148-155 [Mikhailov N.O., Glukhov A.A., Andreev A.A., et al. Clinical and morphological aspects of the use of crushed maral antler slices in the treatment of aseptic soft tissue wounds. Moscow Surgical Journal. 2025; 1: 148–155. https://doi.org/10.17238/2072-3180-2025-1-148-155 (In Russ.).]
  21. Марков П.А., Костромина Е.Ю., Фесюн А.Д., Еремин П.С. Обоснование использования магниточувствительных биоматериалов в клинической практике для стимуляции регенерации костных тканей: обзор литературы. Вестник восстановительной медицины.2024; 23(3): 69–76. https://doi.org/10.38025/2078-1962-2024-23-3-69-76 [Markov P.A., Kostromina E.Yu., Fesyun A.D., Eremin P.S. Rationale of Using Magnetically Sensitive Biomaterials in Bone Tissue Therapy: a Review. Bulletin of Rehabilitation Medicine. 2024; 23(3): 69–76. https://doi.org/10.38025/2078-1962-2024-23-3-69-76 (In Russ.).]
  22. Марков П.А., Еремин П.С., Торлопов М.А., Мартаков И.С., Михайлов В.И. Биофункционализация альгинатного гидрогеля магнитными наночастицами: результаты экспериментального исследования. Вестник восстановительной медицины. 2025; 24(4): 121–129. https://doi.org/10.38025/2078-1962-2025-24-4-121-129 [Markov P.A., Eremin P.S., Torlopov M.A., Martakov I.S., Mikhailov V.I. Use of Magnetic Nanoparticles for Biofunctionalization of Alginate Hydrogel: Experimental Study Findings. Bulletin of Rehabilitation Medicine. 2025; 24(4): 121–129. https://doi.org/10.38025/2078-1962-2025-24-4-121-129 (In Russ.).]



Creative Commons License
The content is available under the Creative Commons Attribution 4.0 License.

©


This is an open article under the CC BY 4.0 license. Published by the National Medical Research Center for Rehabilitation and Balneology.