Genetic lineage tracing of targeted cell populations during enthesis healing

Abstract

Clinically relevant models of rotator cuff tendon injuries in mouse enable the use of genetic tools; lineage tracing suggests that distinct mechanisms of healing are activated with full detachment/repair injuries versus partial tear. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Human Tendon Repair Following Injection of Autologous, Unmodified Stem Cells: A Comprehensive Immunohistochemical Evaluation

“…Organized, slightly undulating type I collagen (Region 1 in Figure 3) is consistent with descriptions of the morphological appearance of a process that is known as "regenerative healing in tendons without scar formation" in the literature (Beredjiklian et al, 2003;Tang et al, 2014;Galatz et al, 2015). Of note, this process does not occur in spontaneous tendon healing which typically results in a localized scar defect adjacent to intact enthesis (Beredjiklian et al, 2003;Tang et al, 2014;Moser et al, 2018). Rather, regenerative healing without scar formation so far has been attributed to fetal tendons (Beredjiklian et al, 2003;Tang et al, 2014;Galatz et al, 2015).…”

Models of tendon development and injury

“…Axin2-expressing cells (indicating resident stem cell lineage) were not found in the scar of the partial tear model, but were the majority of cells detected in the scar of the full tear. Sox9-expressing cells were detected in the articular cartilage of the humeral head, the unmineralized enthesis fibrocartilage, and near the insertion in both the full and partial tear models [113]. These results suggest that distinct cellular mechanisms may operate in response to partial or full tear injuries of the rotator cuff.…”

“…In the partial tear model, gait was not affected, but there was still considerable hypercellular scarring and increased cell density within the healing enthesis. In the same model, lineage tracing showed minimal scleraxis or Sox9 expression in the scar, suggesting that the scar-forming cells were not predominantly derived from tendon, articular cartilage, or unmineralized enthesis [113]. Axin2-expressing cells (indicating resident stem cell lineage) were not found in the scar of the partial tear model, but were the majority of cells detected in the scar of the full tear.…”

“…Surgical injury models of the rotator cuff Surgical models to induce injury have shown promise for identifying factors that influence rotator cuff healing. Partial and full detachment tears of the supraspinatus tendons in adult mice were induced by either insertion of a 26G needle through the central portion of the supraspinatus tendon into the insertion site at the enthesis, or a full transection and surgical repair using sutures [113]. Both injury models healed via scar formation, but the amount of scarring following full detachment and repair led to permanent impairments in gait and disruption of the architecture and organization of the enthesis.…”

Bringing tendon biology to heel: Leveraging mechanisms of tendon development, healing, and regeneration to advance therapeutic strategies

“…For example, Axin2 + tenocytes contribute to healed tissue only following a full, but not partial, enthesis injury in the supraspinatus tendon following surgical repair. 144 Moreover, midbody vs enthesis injuries involve different cell types and may differ in repair mechanisms. As previously mentioned, calcified fibrocartilage formation depends on Hh signaling mediated by Gli1 expression in the mouse enthesis.…”