Enhancement of tendon graft osteointegration using mesenchymal stem cells in a rabbit model of anterior cruciate ligament reconstruction.
OBJECTIVE
To study the effect of coating tendon grafts with mesenchymal stem cells (MSCs) on the rate and quality of graft osteointegration in anterior cruciate ligament (ACL) reconstruction.


METHODS
Animal model.


METHODS
Bilateral ACL reconstructions using hamstring tendon autografts were performed on 48 adult rabbits. Grafts were coated with MSCs in a fibrin glue carrier in one limb, and fibrin glue only in the other. Assessment was done at 2, 4, and 8 weeks. Histologic analysis was carried out using standard and immunohistochemical stains. Biomechanical testing of force and stiffness during loading to ultimate failure was performed.


RESULTS
Control reconstructions showed mature scar tissue with some Sharpey's-like fibers spanning the tendon-bone interface at 8 weeks. The MSC-enhanced reconstructions had large areas of cartilage cells at the tendon-bone junction at 2 weeks. By 8 weeks, a mature zone of cartilage was seen gradually blending from bone into the tendon grafts. This zone stained strongly for type II collagen and showed histologic characteristics similar to normal rabbit ACL insertions. Biomechanically, there was no statistical difference between limbs at 2 and 4 weeks. At 8 weeks, the MSC-enhanced grafts had significantly higher failure load and stiffness.


CONCLUSIONS
Coating of tendon grafts with MSCs results in healing by an intervening zone of cartilage resembling the chondral enthesis of normal ACL insertions rather than collagen fibers and scar tissue. MSC-enhanced ACL reconstructions perform significantly better than controls on biomechanical testing.


CONCLUSIONS
Enhancement of tendon graft osteointegration with MSCs is a novel method offering the potential for more physiologic and biomechanically stronger ligament reconstructions.
Lim
Jit-Kheng
JK
Department of Orthopaedic Surgery, National University Hospital, Singapore, Republic of Singapore. nitrogenbubble@mac.com
Hui
James
J
Li
Li
L
Thambyah
Ashvin
A
Goh
James
J
Lee
Eng-Hin
EH
D000818:Animals; D016118:Anterior Cruciate Ligament / Q000473:pathology / Q000601:surgery*; D045164:Mesenchymal Stem Cell Transplantation; D023421:Models, Animal; D016348:Osseointegration; D011817:Rabbits; D013710:Tendons / Q000637:transplantation*