Mesenchymal Stromal Cell Transplantation Induces Regeneration of Large and Full-Thickness Cartilage Defect of the Temporomandibular Joint

Abstract

Objective: Cartilage damage (CD) in the temporomandibular joint (TMJ) continues being a major problem in maxillofacial field. Evidence suggests that cellular therapy may be used for repairing CD in the TMJ.

Design: A murine model of condyle CD (CCD) was generated in the TMJ to evaluate the capacity of mesenchymal stromal cells (MSCs) to induce cartilage regeneration in CCD. A large CCD was surgically created in a condyle head of the TMJ of C57BL/6 mice. Human MSC embedded into preclotted platelet-rich plasma (PRP) were placed on the surface of CCD. As controls, untreated CCD and exposed TMJ condyle (sham) were used. After 6 weeks, animals were sacrificed, and each mandibular condyle was removed and CCD healing was assessed macroscopically and histologically.

Results: Macroscopic observation of CCD treated with MSC showed the presence of cartilage-like tissue in the CCD site. Histological analysis showed a complete repair of the articular surface with the presence of cartilage-like tissue and subchondral bone filling the CCD area. Chondrocytes were observed into collagen and glycosaminoglycans extracellular matrix filling the repaired tissue. There was no evidence of subchondral bone sclerosis. Untreated CCD showed denudated osteochondral lesions without signs of cartilage repair. Histological analysis showed the absence of tissue formation over the CCD.

Conclusions: Transplantation of MSC induces regeneration of TMJ-CCD. These results provide strong evidence to use MSC as potential treatment in patients with cartilage lesions in the TMJ.

Keywords: MSC; cartilage regeneration; mesenchymal stromal cells; temporomandibular joint.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.

Surgical procedure for condylar cartilage damage CCD. Preauricular shaving and surgical pen designed skin incision (A). Mandibular condylar head and cartilage exposure (arrow) (B). Microsurgical bur (arrow) applied on the head condyle surface for inducing chondral damage (C). Focal chondral defect (head arrows) in the condylar head (D).

Figure 2.

Culture, Characterization, and Differentiation of mesenchymal stromal cells (MSCs). Adherent cells from bone marrow (BM) show fibroblast-like cell morphology (A) and express CD90 and CD105 (B). MSCs differentiate into osteogenic and chondrogenic progenitors (C and D, respectively).

Figure 3.

Evaluation of condylar cartilage damage (CCD) after mesenchymal stromal cell (MSC) transplantation. Condylar head of untreated CCD (A-C). The condylar cartilage is observed before (A, arrow) and after CCD (B, arrow). Chondral defect after 6 weeks (C). The chondral defect remains without evidence of tissue repair (arrow and insert). Condylar head of MSC-treated CCD (D-F). The condylar cartilage is observed before CCD (D, arrow). Chondral defect after CCD (E, arrow), and after 6 weeks post-MSC transplantation (F, arrow). Evidence of cartilage regeneration is observed at the site of CCD were MSC were implanted (F). New cartilage-like tissue is observed filling the chondral defect (arrow and insert). Results are representative of 4 CCD (one joint in eachTMJ ) in each group, all of which had similar results. TMJ = temporo mandibular joint.

Figure 4.

Histological analysis from untreated or mesenchymal stromal cell (MSC)-treated condylar cartilage damage (CCD). After 6 weeks of MSC transplantation, untreated or MSC-treated CDD lesions were processed for histological examination by hematoxylin and eosin (H&E) staining. An area of cartilage discontinuity (bucket defect) with denuded subchondral area is observed in untreated CDD lesions (A). Alcian blue staining show the absence of extracellular matrix formation in the CDD area (B). CDD transplanted with MSCs showed new a continuous cartilaginous tissue, containing chondrocytes, and ECM (C). The CCD defect was completely covered by newly cartilage and bone at the top of the condyle. A thin subchondral plate and trabeculae is evidenced at the site of CDD. The repaired cartilage defect shows a strong and homogenous Alcian blue staining, which indicates the presence of extracellular matrix with proteoglycan content (D). Representative H&E and Alcian blue staining from condyle slices are showed. Mankin scores of MSC-treated CCD was lower than that of untreated CCD (E). Data are shown as the average of Mankin scores performed by 3 independent observers.