Comparative study on functional effects of allotransplantation of bone marrow stromal cells and adipose derived stromal vascular fraction on tendon repair: a biomechanical study in rabbits

Abstract

Objective: Tendon never returns to its complete biological and mechanical properties after repair. Bone marrow and, recently, adipose tissue have been used as sources of mesenchymal stem cells which have been proven to enhance tendon healing. In the present study, we compared the effects of allotransplantation of bone marrow derived mesenchymal stromal cells (BMSCs) and adipose derived stromal vascular fraction (SVF) on tendon mechanical properties after experimentally induced flexor tendon transection.

Materials and methods: In this experimental study, we used 48 adult male New Zealand white rabbits. Twelve of rabbits were used as donors of bone marrow and adipose tissue, the rest were divided into control and treatment groups. The injury model was a unilateral complete transection of the deep digital flexor tendon. Immediately after suture repair, 4×10(6)cells of either fresh SVF from enzymatic digestion of adipose tissue or cultured BMSCs were intratendinously injected into tendon stumps in the treatment groups. Controls received phosphate-buffered saline (PBS). Immobilization with a cast was continued for two weeks after surgery. Animals were sacrificed three and eight weeks after surgery and tendons underwent mechanical evaluations. The differences among the groups were analyzed using the analysis of variance (ANOVA) test followed by Tukey's multiple comparisons test.

Results: Stromal cell transplantation resulted in a significant increase in ultimate and yield loads, energy absorption, and stress of repairs compared to the controls. However, there were no statistically significant changes detected in terms of stiffness. In comparison, we observed no significant differences at the third week between SVF and BMSCs treated tendons in terms of all load related properties. However, at the eighth week SVF transplantation resulted in significantly increased energy absorption, stress and stiffness compared to BMSCs.

Conclusion: The enhanced biomechanical properties of repairs in this study advocates the application of adipose derived SVF as an excellent source of multipotent cells instead of traditional BMSCs and may seem more encouraging in cell-based therapy for tendon injuries.

Keywords: Adipose Tissue; Bone Marrow; Tendon; Tensile Strength; Transplantation.

Fig 1

A. Spindle-shaped fibroblast-like mesenchymal stromal cells isolated from rabbit bone marrow. B. Nucleated cells in stromal vascular fraction isolated from rabbit adipose tissue (scale bar =100 μm).

Fig 2

Intraoperative photographs illustrate: A. exposed deep digital flexor tendon, B. modified Kessler suture placement after complete transection of the tendon and C. intratendinous injection of either stromal cells or phosphate-buffered saline (PBS) in tendon stumps.

Fig 3

The load values of repairs at the maximum load point at three and eight weeks after surgery. Column heights and error bars represent the group mean and SD. *, †, ‡; Different symbols indicate significant differences among the groups (p<0.05).

Fig 4

The load values of repairs at the yield point at three and eight weeks after surgery. Column heights and error bars represent the group mean and SD. *, †, ‡; Different symbols indicate significant differences among the groups (p<0.05).

Fig 5

The energy absorption capacity of repairs up to the maximum load point at three and eight weeks after surgery. Column heights and error bars represent the group mean and SD. *, †, ‡; Different symbols indicate significant differences among the groups (p<0.05).

Fig 6

The ultimate stress of repairs at three and eight weeks after surgery. Column heights and error bars represent the group mean and SD. *, †, ‡; Different symbols indicate significant differences among the groups (p<0.05).

Fig 7

The ultimate strain of repairs at three and eight weeks after surgery. No statistically significant differences were found among the groups (p>0.05). Column heights and error bars represent the group mean and SD.

Fig 8

The stiffness of repairs at three and eight weeks after surgery. Column heights and error bars represent the group mean and SD. *, †, ‡; Different symbols indicate significant differences among the groups (p<0.05).