Differences between the Cell Populations from the Peritenon and the Tendon Core with Regard to Their Potential Implication in Tendon Repair

Abstract

The role of intrinsic and extrinsic healing in injured tendons is still debated. In this study, we characterized cell plasticity, proliferative capacity, and migration characteristics as proxy measures of healing potential in cells derived from the peritenon (extrinsic healing) and compared these to cells from the tendon core (intrinsic healing). Both cell populations were extracted from horse superficial digital flexor tendon and characterized for tenogenic and matrix remodeling markers as well as for rates of migration and replication. Furthermore, colony-forming unit assays, multipotency assays, and real-time quantitative polymerase chain reaction analyses of markers of osteogenic and adipogenic differentiation after culture in induction media were performed. Finally, cellular capacity for differentiation towards a myofibroblastic phenotype was assessed. Our results demonstrate that both tendon- and peritenon-derived cell populations are capable of adipogenic and osteogenic differentiation, with higher expression of progenitor cell markers in peritenon cells. Cells from the peritenon also migrated faster, replicate more quickly, and show higher differentiation potential toward a myofibroblastic phenotype when compared to cells from the tendon core. Based on these data, we suggest that cells from the peritenon have substantial potential to influence tendon-healing outcome, warranting further scrutiny of their role.

Tendon injury and repair – A perspective on the basic mechanisms of tendon disease and future clinical therapy

“…The extrinsic compartment envelops the second (intrinsic) compartment, which is often referred to as the ''tendon core". The tendon core consists of densely packed Type-I collagen matrix and the fibroblastic cells that maintain it [50]. Although increasingly realized to have distinct functions in the context of tendon disease and repair, the physiological roles of many of the cells within both compartments and possible communication between the compartments is still poorly understood [50][51][52][53][54].…”

“…''intrinsic tendon core structures" that form the basic functional unit of the tendon [19]. In turn, fascicles, crosslinked to various degrees, assemble into tissue level constructs, surrounded by the epitenon (mid-level extrinsic compartment) [50,52]. Finally, the highest level structural organization of tendon tissue reflects the organ that may or may not be surrounded by paratenon [19].…”

“…Our current understanding is that the tendon core is occupied by tendon fibroblasts (also widely referred to as tenocytes), with more diverse cell populations found in the tissue barriers that comprise the extrinsic compartment of the tendon [50,52]. Within a healthy tendon core, tenocytes attach to a highly ordered fibrillar collagen matrix (ECM) (Fig.…”

The past, present and future in scaffold-based tendon treatments

“…Perivascular cells are found in the walls of internal and external tendon capillaries and have been identified as cells that could have a regenerative capacity. They are expressing both mature tendon and stem cell related markers, after being isolated and cultured in vitro [68,69]. Further small populations of mesenchymal stem cells (MSC) have also been identified to be present in both equine and human tendons, although they are generally not recognised as a site for potential stem cell source, due to their poor availability [70].…”

Restricted differentiation potential of progenitor cell populations obtained from the equine superficial digital flexor tendon (SDFT)

“…Cells obtained from the peritenon of mouse Achilles tendon demonstrated decreased clonogenicity compared to the tendon core and limited osteogenic differentiation 12. In the equine SDFT, peritenon cells displayed decreased clonogenicity and both osteogenic and adipogenic differentiation, but were reported to have increased proliferation and increased expression of progenitor cell markers 15. Tendons are relatively poorly vascularized16 and tendon cells reside within a hypoxic environment.…”