Abstract

Tendons are fibrous bands of connective tissue, transmitting force from muscle to bone. Their healing capacity is very limited. Tendons do not regenerate after trauma or degeneration; scar tissue usually fills the site of damage. The so called “tenocytes” forming tendon tissue are poorly characterized and considered to be of mesodermal origin, like bone fat and cartilage. We have previously shown that tendon perivascular cells express both tendon- and stem cell associated markers, suggesting that these cells represent a population of tendon progenitor cells.These cells express markers associated with stem cells less committed than mesenchymal stem cells, such as Nestin, Sox2, C-myc and Klf4. In vitro they can give rise to electrophysiologically active neurons, to osteoblasts and adipocytes. In vivo, tendon cells express neuronal markers like Doublecortin, GAP43 and a variety of neuropeptides such as substance P and BDNF . Using a Sox10cre mouse model, we observe that the majority of tendon cells originate from cells expressing Sox10, suggesting a neural crest origin of tendon tissue. Regarding the tendon stem/ progenitor cell niche, we hypothesize that there is a selective barrier between the blood flow and the tendon perivascular cells, establishing a microenvironment allowing the cells to remain in their undifferentiated status. By immunohistochemistry qRT-PCR on human and mouse tissue we show the expression of the tight junction associated markers Claudin 1, 3, 5 and Occludin in tendon vascular endothelial cells. These proteins are responsible for building up the blood brain barrier and the blood retina barrier. By injection of a 10kD dextrane tracer to mouse tail veines, we show that this barrier is functional. These findings may lead to a new understanding of tendon disorders like tendinopathy and to novel strategies in stem cell based tissue engineering approaches.