Effect of Bone Marrow Aspirate Concentrate-Platelet-Rich Plasma on Tendon-Derived Stem Cells and Rotator Cuff Tendon Tear

Abstract

Bone marrow aspirate concentrates (BMACs) and platelet-rich plasma (PRP) are good sources to control the differentiation of tendon-derived stem cells (TDSCs), but there has been no study about the effect of the BMAC-PRP complex on TDSCs and tendinopathy. The aim of this study was to investigate the effect of BMAC-PRP on the TDSCs and to find the therapeutic effect of BMAC-PRP on the rotator cuff tendon tear. The chondrogenic and osteogenic potential of TDSCs decreased, but the adipogenic potential of TDSCs revealed no significant difference when they were cocultured with BMAC-PRP. Cell proliferation was significantly greater in TDSCs cocultured with BMAC-PRP than in TDSCs. The degree of wound closure (percentage) was different between TDSCs and TDSCs with BMAC-PRP. There was no significant difference in expression of collagen type I and type III in immunocytochemical staining in the presence of BMAC-PRP. Initial visual analog scale (VAS) score was 5.8 ± 1.9, which changed to 5.0 ± 2.3 at 3 weeks and 2.8 ± 2.3 at 3 months after the BMAC-PRP injection (p < 0.01). The American Shoulder Elbow Surgeon score changed from 39.4 ± 13.0 at baseline to 52.9 ± 22.9 at 3 weeks and 71.8 ± 19.7 at 3 months after the injection (p < 0.01). The initial torn area of the rotator cuff tendon was 30.2 ± 24.5 mm2, and this area was reduced to 22.5 ± 18.9 mm2 at 3 months, but the change was not significant (p > 0.05). The data indicate that BMAC-PRP enhances the proliferation and migration of TDSCs and prevents the aberrant chondrogenic and osteogenic differentiation of TDSCs, which might provide a mechanistic basis for the therapeutic benefits of BMAC-PRP for rotator cuff tendon tear.

Figure 1.

Tear size was measured by width (mm) and depth (mm) (A), and the bone marrow aspirate concentrate–platelet-rich plasma (BMAC–PRP) complex injection was done under ultrasound guidance (B).

Figure 2.

Immunocytochemical staining for tendon-derived stem cells (TDSCs) and expression of surface antigens for identification of TDSCs. OCT4, octamer-binding transcription factor 4; SSEA4, stage-specific embryonic antigen-4; FITC, fluorescein isothiocyanate; PE, phycoerythrin. Scale bars: 50 μm.

Figure 3.

Multidifferentiation potential of tendon-derived stem cells (TDSCs) was confirmed by the osteogenic and adipogenic induction. Osteogenic potential of TDSCs decreased, but the adipogenic potential of TDSCs revealed no significant difference when they were cocultured with bone marrow aspirate concentrate–platelet-rich plasma (BMAC–PRP) complex.

Figure 4.

Chondrogenic differentiation potential of tendon-derived stem cells (TDSCs) was confirmed by the chondrogenic induction. Chondrogenic potential of TDSCs decreased when they were cocultured with bone marrow aspirate concentrate–platelet-rich plasma (BMAC–PRP) complex.

Figure 5.

Cell proliferation measured using Cell Counting Kit-8^® (CCK-8) assay. After 1 day of incubation, cell proliferation was nearly identical in tendon-derived stem cells (TDSCs) and TDSCs cocultured with bone marrow aspirate concentrate–platelet-rich plasma (BMAC–PRP) complex. Cell proliferation was significantly greater in TDSCs cocultured with BMAC–PRP than in TDSCs at 3, 5, 7, and 9 days. *p < 0.05.

Figure 6.

As a surrogate read for wound healing, tendon-derived stem cells (TDSCs) were separated by scratching, and the extents of migration of the two fronts toward each other were observed at 24 and 48 h. Degree of wound closure (percentage) was quantified by the ImageJ program. Wound healing was significantly different between TDSCs and TDSCs with bone marrow aspirate concentrate–platelet-rich plasma (BMAC–PRP) complex. *p < 0.05.

Figure 7.

Immunocytochemical staining of collagen type I and type III. There was no significant difference in expression of collagen type I and type III in immunocytochemical staining in the presence of bone marrow aspirate concentrate–platelet-rich plasma (BMAC–PRP) complex. DAPI, 4′,6-diamidino-2-pheylindole.

Figure 8.

Visual analog scale (VAS) and American Shoulder Elbow Surgeon (ASES) score 3 weeks and 3 months after bone marrow aspirate concentrate–platelet-rich plasma (BMAC–PRP) complex injection.