Detection of slow-cycling and stem/progenitor cells in different regions of rat Achilles tendon: response to treadmill exercise

Abstract

Tendons generally exhibit poor healing capacity, probably due to slow cell regeneration potential and low vascularization. The potential to regenerate may partly be due to activation of stem/progenitor cells localized in the tendon or its vicinity. In the present study, we attempted to determine where in the rat Achilles tendon stem/progenitor cells reside and to investigate the effect of exercise on cell proliferation in the in vivo situation. We used bromodeoxyuridine (BrdU) labelling to investigate proliferation and label-retaining cells (i.e. slow-cycling cells) in non-exercised and exercised rats, in combination with immunostaining of the stem cell marker nucleostemin. Rat Achilles tendons were harvested 14, 28, 56 and 105 days after BrdU administration. We found the proportion of stem/progenitor cells to be twice as high in the distal tendon (DT) compared with the mid/proximal tendon (MPT) and that paratenon/endotenon regions appear to host a pool of existing stem/progenitor cells. Exercise increased the BrdU-stained cell population after 14 days only (DT region p = 0.032, MPT p = 0.065), indicating effect mainly on more differentiated cells, since the nucleostemin-positive cells (i.e. stem/progenitor cells) remained unaffected in the intact Achilles tendon. Stem/progenitor cells exist in several areas of the rat Achilles tendon which implies a possible stem cell regeneration pool of different origins. The distal region has twice the amount of stem/progenitor cells compared with the mid/proximal region, indicating a potentially higher stem cell activity in this tissue. Daily moderate exercise (treadmill running) mainly improves in vivo cell proliferation in rapidly proliferating cells, whereas the stem/progenitor pool remains constant.