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

Abstract

Purpose: 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.

Method: 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.

Results: 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.

Conclusion: 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.