Use of Human Placenta-Derived Cells in a Preclinical Model of Tendon Injury

Emerging data suggest that human cells derived from extraembryonic tissues may have favorable musculoskeletal repair properties. The purpose of this study was to determine whether the injection of human placenta-derived mesenchymal-like stromal cells, termed placental expanded cells (PLX-PAD), would improve tendon healing in a preclinical model of tendinopathy.Methods:Sixty male Sprague-Dawley rats underwent bilateral patellar tendon injection with either saline solution (control) or PLX-PAD cells (2 × 10⁶ cells/100 L) 6 days after collagenase injection to induce tendon degeneration. Animals were killed at specific time points for biomechanical, histological, and gene expression analyses of the healing patellar tendons.Results:Biomechanical testing 2 weeks after the collagenase injury demonstrated better biomechanical properties in the tendons treated with PLX-PAD cells. The load to failure of the PLX-PAD-treated tendons was higher than that of the saline-solution-treated controls at 2 weeks (77.01 ± 10.51 versus 58.87 ± 11.97 N, p = 0.01). There was no significant difference between the 2 groups at 4 weeks. There were no differences in stiffness at either time point. Semiquantitative histological analysis demonstrated no significant differences in collagen organization or cellularity between the PLX-PAD and saline-solution-treated tendons. Gene expression analysis demonstrated higher levels of interleukin-1β (IL-1β) and IL-6 early in the healing process in the PLX-PAD-treated tendons.Conclusions:Human placenta-derived cell therapy induced an early inflammatory response and a transient beneficial effect on tendon failure load in a model of collagenase-induced tendon degeneration.Clinical Relevance:Human extraembryonic tissues, such as the placenta, are an emerging source of cells for musculoskeletal repair and may hold promise as a point-of-care cell therapy for tendon injuries.