The tendon interfascicular basement membrane provides a vascular niche for CD146+ pericyte cell subpopulations

Abstract

The interfascicular matrix (IFM) is critical to the mechanical adaptations and response to load in energy-storing tendons, such as the human Achilles and equine superficial digital flexor tendon (SDFT). We hypothesized that the IFM is a tendon progenitor cell niche housing an exclusive cell subpopulation. Immunolabelling of equine SDFT was used to identify the IFM niche, localising expression patterns of CD31 (endothelial cells), CD146 (IFM cells) and LAMA4 (IFM basement membrane marker). Magnetic-activated cell sorting was employed to isolate and compare in vitro properties of CD146+ and CD146- subpopulations. CD146 demarcated an exclusive interfascicular cell subpopulation that resides in proximity to a basal lamina which forms interconnected vascular networks. Isolated CD146+ cells exhibited limited mineralization (osteogenesis) and lipid production (adipogenesis). This study demonstrates that the IFM is a unique tendon cell niche, containing a vascular-rich network of basement membrane, CD31+ endothelial cells and CD146+ cell populations that are likely essential to tendon structure- and/or function. Interfascicular CD146+ subpopulations did not exhibit stem cell-like phenotypes and are more likely to represent a pericyte lineage. Previous work has shown that tendon CD146 cells migrate to sites of injury, therefore mobilisation of endogenous tendon IFM cell populations may promote intrinsic repair.