Pdgfrß+ lineage cells transiently increase at the site of Achilles tendon healing.

ABSTRACT

The purpose of this study was to track platelet-derived growth factor receptor-ß (Pdgfr-ß) lineage cells at the site of Achilles tendon injury over time. Pdgfr-ß-CreERT2Ai9 mice were generated to track Pdgfr-ß lineage cells in adult mice. A surgical Achilles transection injury model was employed to examine the presence of Pdgfr-ß lineage cells in the healing tendon over time, with five mice per time point at 3, 7, 14, 28, and 56 days postoperatively. Histology and immunohistochemistry for tdTomato (Pdgfr-ß lineage cells), PCNA (proliferating cell nuclear antigen, cell proliferation), and α-SMA (α-smooth muscle actin, myofibroblasts) were performed. The percentage of cells at the healing tendon site staining positive for tdTomato and PCNA were quantified. Over 75% of cells at the injury site were Pdgfr-ß lineage cells at Days 3, 7, and 14, and this percentage decreased significantly by Days 28 and 56 postinjury. Cell proliferation at the injury site peaked on Day 7 and decreased thereafter. Immunohistochemistry for α-SMA demonstrated minimal colocalization of myofibroblasts with Pdgfr-ß lineage cells. This study demonstrates that in a mouse model of Achilles tendon injury, Pdgfr-ß lineage cells' presence at the injury site is transient. Thus, we conclude that they are unlikely to be the cells that differentiate into myofibroblasts and directly contribute to tendon fibrous scar formation. Clinical Significance: This study provides some insight into the presence of Pdgfr-ß lineage cells (including pericytes) following Achilles injury, furthering our understanding of tendon healing.