Preclinical evaluation of the efficacy of cell technologies in restoring the integrity of the rectal sphincter apparatus muscle tissue

The article presents the results of experimental studies on the efficacy in addressing cell therapy for structural and functional impairments of muscular tissue integrity in a surgically induced model of encopresis. Based on morphological and morphometric studies, it was established that local (intersphincteric) administration of smooth muscle cells (SMCs), multipotent mesenchymal stromal cells (MMSCs) from adipose tissue (AT) and bone marrow (BM), as well as leiomyocyte-like cells (myogenically differentiated AT-MMSCs), enhances the regenerative processes of the smooth muscle component of the rectal wall. In the injury zone, SMC proliferation is observed, leading to the formation of a hyperplastic muscle layer (both circular and longitudinal). The most pronounced changes in the thickness of the smooth muscle layer are noted when using cell products based on SMCs and AT-MMSCs. Further research into the regenerative potential of MMSCs will expand our understanding of the cells’ potential to participate in the restoration of not only visceral but also striated muscle tissue, and will facilitate the scientifically grounded application of cell technologies in clinical practice.

1. Salemi S., Prange J. A., Baumgartner V., Mohr‑Haralampieva D., Eberli D. Adult stem cell sources for skeletal and smooth muscle tissue engineering. Stem Cell Research and Therapy, 2022, vol. 13, no. 1, art. 156. https://doi.org/10.1186/s13287-022-02835-x

2. Jung C., Han J. W., Lee S.-J., Kim K. H., Oh J. E., Bae S. [et al.]. Novel directly reprogrammed smooth muscle cells promote vascular regeneration as microvascular mural cells. Circulation, 2025, vol. 151, no. 15, pp. 1076–1094. https://doi.org/10.1161/CIRCULATIONAHA.124.070217

3. Yuzefovich N. A., Yudina O. A., Mel’nikov I. A., Studenikina T. M. Feature of the expression of vimentin, desmin, vascular endothelial growth factor in an aortic media in normal and abdominal aortic aneurysm. Meditsinskie novosti [Medical news], 2017, no. 8, pp. 71–76 (in Russian).

4. Cao G., Xuan X., Hu J., Zhang R., Jin H., Dong H. How vascular smooth muscle cell phenotype switching contributes to vascular disease. Cell Communication and Signaling, 2022, vol. 20, no. 1, art. 180. https://doi.org/10.1186/s12964-022-00993-2

5. Azar P., Jarr K.-U., Gomez D., Jørgensen H. F., Leeper N. J., Bochaton-Piallat M.-L. Smooth muscle cells in atherosclerosis: essential but overlooked translational perspectives. European Heart Journal, 2025, vol. 46, no. 45, pp. 4862–4875. https://doi.org/10.1093/eurheartj/ehaf337

6. Kim M., Oh B.-Y., Lee J.-S., Yoon D., Kim Y.-R., Chun W., Kim J. W., Son I. T. Differentiation of adipose-derived stem cells into smooth muscle cells in an internal anal sphincter-targeting anal incontinence rat model. Journal of Clinical Medicine, 2023, vol. 12, no. 4, art. 1632. https://doi.org/10.3390/jcm12041632

7. Sivaraman S., Hedrick J., Ismail S., Slavin C., Rao R.R. Generation and characterization of human mesenchymal stem cell-derived smooth muscle cells. International Journal of Molecular Sciences, 2021, vol. 22, no.19, art. 10335. https://doi.org/10.3390/ijms221910335

8. Gu X., Hong X., Bras A. Le, Nowak W. N., Bhaloo Sh. I., Deng J., Xie Y., Hu Y., Ruan X. Z., Xu Q. Smooth muscle cells differentiated from mesenchymal stem cells are regulated by microRNAs and suitable for vascular tissue grafts. The Journal of Biological Chemistry, 2018, vol. 293, no. 21, pp. 8089–8102. https://doi.org/10.1074/jbc.RA118.001739

9. Ahmad R. E., Mokhtar A. H., Mohamed Al-Fayyadh M. Z., Nam H. Y., Aziz A., Mansor A., Kamarul T. Effect of allogenic mesenchymal stem cell injection on functional repair outcomes following skeletal muscle laceration injury. Biomedicines, 2025, vol. 13, no. 11, art. 2810. https://doi.org/10.3390/biomedicines13112810

10. Galindo S., López-Paniagua M, de la Mata A., Herreras J. M., García-Vázquez C., Marceñido B., Rey E., HigueraBarón C., Calonge M., Nieto-Miguel T. Bone marrow-versus adipose tissue-derived mesenchymal stem cells for corneal failure in an experimental model of limbal stem cell deficiency. Experimental Eye Research, 2026, vol. 262, art. 110737. https://doi.org/10.1016/j.exer.2025.110737

11. Lethager L. L., Bangsgaard S., Johansen E. M., Qayyum A. A., Christensen J. P., Ekblond A., Norgaard M. J., Hojgaard L. D. In vitro assays for investigating the immunomodulatory properties of human mesenchymal stromal cells. Stem Cell Research and Therapy, 2026, vol. 17, no. 1, art. 102. https://doi.org/10.1186/s13287-026-04920-x

12. Yurkina E. G., Krivenko S. I., Smol’nikova V. V., Primakova E. A., Nazarova E. A., Symanovich A. A., Dedyulya N. I., Romanova I. A., Efimov D. Yu., Shcherba A. E., Rummo O. O. Comparative analysis of the profile of expression of molecular markers of mesenchymal stem cells obtained from placental-umbilical cord complex tissues, adipose tissue and bone marrow. Doklady Natsional’noi akademii nauk Belarusi = Doklady of the National Academy of Sciences of Belarus, 2025, vol. 69, no. 4, pp. 314–321 (in Russian).

13. Li C.-Y., Wu X.-Y., Tong J.-B., Yang X.-X., Zhao J.-L., Zheng Q.-F., Zhao G.-B., Ma Z.-J. Comparative analysis of human mesenchymal stem cells from bone marrow and adipose tissue under xeno-free conditions for cell therapy. Stem Cell Research and Therapy, 2015, vol. 6, no. 1, art. 55. https://doi.org/10.1186/s13287-015-0066-5

14. Levchuk K. A., Malashicheva A. B. Regional functional heterogeneity of aortic smooth muscle cells in rats. Russian Journal of Developmental Biology, 2017, vol. 48, no. 3, pp. 219–223. https://doi.org/10.1134/S1062360417030080

15. Kulinich S. S., Gain Yu. M., Shakhrai S. V., Vladimirskaya T. E. Animal model of anal incontinence in rats. Nauchnye issledovaniya v meditsine: ot teorii k praktike: sbornik nauchnykh trudov nauchno-prakticheskoi konferentsii, posvyashchennoi 85-letiyu BelMAPO, 25 noyabrya 2016 goda [Scientific research in medicine: from theory to practice: a collection of scientific papers from the scientific and practical conference dedicated to the 85th anniversary of the Belarusian Medical Academy of Postgraduate Education, November 25, 2016]. Minsk, 2016, pp. 436–441 (in Russian).