Tissue repairing following amniotic stem cell transplantation in sheep tendon lesions

The repairing process occurring in tendon lesions following amniotic epithelial stem cells (AESC) transplantation has been investigated. Experimental lesions were induced in both calcaneal tendons of 5 sheep by injecting 400 I.U. of collagenase. 15 days later AESC were injected under ultrasound guidance into the enzyme-induced lesion of one limb while saline was injected in the controlateral lesion (control). Tendons were harvested from euthanized sheep 7 and 30 days following AESC transplantation. Histological examination of tendons isolated 7 days after the treatment revealed bilateral inflammatory signs with loss of matrix organisation and collagen fibres irregularly oriented. Clear signs of tendon healing were recorded 30 days after stem cell transplantation. The site of injection was in fact characterized by a diffuse presence of repairing connective cells with frequent mitotic pictures and accumulating collagen fibres within the extracellular matrix that started to be organised in parallel arrays oriented along the longitudinal axis of the tendon. Amniotic stem cells, still clearly detectable at this time, did not show any proliferation but they were frequently recorded in close proximity of groups of actively proliferating connective cells. AESC did not cause any detectable inflammatory infiltrations. No clear signs of tendon healing were recorded in the controlateral control tendons were the collagenase-induced lesions were still clearly visible, little cell proliferation was present and collagen fibres were randomly oriented in the extracellular matrix. This research demonstrates that molecular and cellular responses occurring during tendon healing are markedly improved by the presence of allotrasplanted AESC.