Autologous bone marrow-derived mesenchymal stem cells provide complete regeneration in a rabbit model of the Achilles tendon bundle rupture.

Abstract

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 sixmonths 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.