To ascertain the role of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in the tendon regeneration.
The study was conducted on 58 Achilles tendons from 29 laboratory Chinchilla adult rabbits. The central bundles of 48 tendons were partially removed and substituted with a tissue-engineered construct consisting of a collagen sponge either loaded with BM-MSCs (n = 24) or cell free (n = 24), placed inside a Vicryl mesh tube. The ends of the resected tendon were inserted in the construct to reach a direct contact with the sponge and sutured to the tube. The animals were sacrificed three and six months post-surgery. Ten intact tendons from five rabbits were used as an untreated control. The tissue samples (n = 30) were stained with haematoxylin and eosin, Picrosirius red, primary antibodies to collagen types I and III and studied by bright-field, phase-contrast, polarized light, and scanning electron microscopies followed by semi-quantitative morphometry.
Six months results of cell-loaded scaffolds demonstrated parallel collagen fibres, spindle-shaped tenocytes, and neoangiogenesis. In the control cell-free group, the injured areas were filled with a nonspecific fibrotic tissue with minor foci of incomplete regeneration. The biomechanical tests of 28 tendons taken from 14 rabbits showed that the stiffness of the cell-based reconstructed tendons increased to 98% of the value for the intact samples.
The obtained results support the hypothesis that the application of BM-MSCs in a tissue-engineered tendon construct leads to the restitution of the tendon tissue.
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This work was supported by the N.F. Gamaleya National Research Center for Epidemiology & Microbiology of the Ministry of Health of the Russian Federation in the part of preparing MSCs and tissue-engineered constructs, by the Ministry of Science and Higher Education within the State assignment FSRC «Crystallography and Photonics» RAS in the part of the SEM analysis, by the Ministry of Science and Higher Education of the Russian Federation under the grant agreement No. 075–15-2021–596 (Megagrant, 2020–220-08–5262) in the part of the biomechanical studies, by the Russian Foundation for Basic Research (Project 18–29-06059) in the part of animal experiments and histological studies.
This study was approved by the institutional review board. The experiments were performed in accordance with the European Convention (Strasbourg, 1986) and the Helsinki Declaration of the World Medical Association on the Humane Treatment of Animals (2000).
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Chailakhyan, R.K., Kon, E., Shekhter, A.B. et al. Autologous bone marrow-derived mesenchymal stem cells provide complete regeneration in a rabbit model of the Achilles tendon bundle rupture. International Orthopaedics (SICOT) (2021). https://doi.org/10.1007/s00264-021-05168-1
- Tissue engineering
- Tendon tissue
- Tendon injury
- Cell therapy
- Cell-loaded scaffolds