TMJ derived Stem/Progenitor Cells: Properties, Clonal Characteristics, and Regeneration Potential

Objective: Treatment options for TMJ degeneration are limited and do not promote regeneration.  One of the critical barriers of TMJ regeneration is the deficient understanding of whether the TMJ harbors stem/progenitor cells. Our goals were to: 1) isolate and characterize putative TMJ stem/progenitor cells, and 2) determine the potential application of TMJ stem/progenitor cells for regeneration.  We hypothesized that TMJ harbors stem/progenitor-like cells that are consistent with other skeletal stem/progenitor cells with a capacity for regeneration of multiple tissues.

Method: Primary TMJ disc cells (DCs) and mandible condyle cells (MCCs) were isolated from rat and human TMJs.  Donor-matched bone marrow stem/stromal cells (BMSCs) served as controls.  Heterogeneous DCs and MCCs were characterized using quantitative RT-PCR, immunocytochemistry, colony forming assay, flow cytometry and examined for multipotency.  A total of 64 clonal progenies were isolated and individually characterized for  multipotency.  In a parallel experiment, a surgical TMJ regeneration model in rabbits was performed with complete excision of the TMJ condyle and replaced with anatomically correct bioscaffolds.

 Result: RT-PCR analysis showed DCs and MCCs had distinct gene expression profiles and cell surface markers in comparison to donor matched BMSCs.  In chemically defined media, DCs and MCCs underwent osteogenesis (alizarin red+, Runx2+, alkaline phosphatase+ and osteocalcin+), adipogenesis (PPARɣ2+ and Oil-red O+), and chondrogenesis in pellet cultures (toluidine blue+, safranin O+, alcian blue+, Collagen type II+, and aggrecan+).  DCs and MCCs formed single-cell colonies by colony-forming assay, with characteristic morphology, size and protein expression patterns.  Clonal progenies showed vast differences in differentiation potential. Rabbits with critical size TMJ condyle defects showed compromised chewing patterns.  Rabbits with anatomically correct TMJ bioscaffolds showed functional recovery.

Conclusion: TMJ disc and condyle harbor distinct stem/progenitor-like cells that may participate in TMJ tissue homeostasis and regeneration.