Mesenchymal stem cells from a hypoxic culture improve and engraft Achilles tendon repair

Bone marrow-derived mesenchymal stem cells (MSCs) from humans cultured under hypoxic conditions increase bone healing capacity.

Rat MSCs cultured under hypoxic conditions increase the tendon healing potential after transplantation into injured Achilles tendons.

Controlled laboratory study.

Biomechanical testing, histological analysis, and bromodeoxyuridine (BrdU) labeling/collagen immunohistochemistry were performed to demonstrate that augmentation of an Achilles tendon rupture site with hypoxic MSCs increases healing capacity compared with normoxic MSCs and controls. Fifty Sprague-Dawley rats were used for the experiments, with 2 rats as the source of bone marrow MSCs. The cut Achilles tendons in the rats were equally divided into 3 groups: hypoxic MSC, normoxic MSC, and nontreated (vehicle control). The uncut tendons served as normal uncut controls. Outcome measures included mechanical testing in 24 rats, histological analysis, and BrdU labeling/collagen immunohistochemistry in another 24 rats.

The ultimate failure load in the hypoxic MSC group was significantly greater than that in the nontreated or normoxic MSC group at 2 weeks after incision (2.1 N/mm(2) vs 1.1 N/mm(2) or 1.9 N/mm(2), respectively) and at 4 weeks after incision (5.5 N/mm(2) vs 1.7 N/mm(2) or 2.7 N/mm(2), respectively). The ultimate failure load in the hypoxic MSC group at 4 weeks after incision (5.5 N/mm(2)) was close to but still significantly less than that of the uncut tendon (7.2 N/mm(2)). Histological analysis as determined by the semiquantitative Bonar histopathological grading scale revealed that the hypoxic MSC group underwent a significant improvement in Achilles tendon healing both at 2 and 4 weeks when compared with the nontreated or normoxic MSC group via statistical analysis. Immunohistochemistry further demonstrated that the hypoxic and normoxic MSC groups had stronger immunostaining for type I and type III collagen than did the nontreated group both at 2 and 4 weeks after incision. Moreover, BrdU labeling of MSCs before injection further determined the incorporation and retention of transplanted cells at the rupture site.

Transplantation of hypoxic MSCs may be a better and more readily available treatment than normoxic MSCs for Achilles tendon ruptures.

The present study provides evidence that transplantation of hypoxic MSCs may be a promising therapy for the treatment of Achilles tendon ruptures.