Treating Achilles tendon rupture in rats with bone-marrow-cell transplantation therapy.
BACKGROUND
Bone marrow cells possess multipotentiality and have been used for several treatments. We hypothesized that bone marrow cells might differentiate into regenerated tendon and that several cytokines within bone marrow cells might accelerate tendon healing. Therefore, we treated Achilles tendon ruptures in a rat model with transplantation of whole bone marrow cells.


METHODS
Nine F344/Nslc (Fisher) rats were the source of bone marrow cells and mesenchymal stem cells as well as normal Achilles tendons. Eighty-seven Fisher rats were used for the experiments. The rats were divided into three groups: the BMC group (bone marrow cells injected around the tendon), the MSC group (mesenchymal stem cells injected around the tendon), and the non-treated control group (incision only). Outcome measures included mechanical testing, collagen immunohistochemistry, histological analysis, and reverse transcription-polymerase chain reaction to detect expression of transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF).


RESULTS
The ultimate failure load in the BMC group was significantly greater than that in the non-treated or the MSC group at seven days after incision (3.8 N vs. 0.9 N or 2.1 N, p < 0.016) and at fourteen days after incision (10.2 N vs. 6.1 N or 8.2 N, p < 0.016). The ultimate failure load in the BMC group at twenty-eight days after incision (33.8 N) was the same as that of normal tendon (34.8 N). The BMC group demonstrated stronger staining for type-III collagen at seven days after incision and stronger staining for type-I collagen at twenty-eight days than did the MSC group. Expression of TGF-β and VEGF in the BMC group was significantly increased compared with that in the other groups at four days after incision (TGF-β: 1.6 vs. 1.3 or 0.6, p < 0.01; VEGF: 1.7 vs. 1.1 or 0.9, p < 0.01).


CONCLUSIONS
Transplantation of whole bone marrow cells may be a better and more readily available treatment for Achilles tendon rupture than cultured mesenchymal stem cells.
Department of Orthopaedic Surgery, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka 570-8506, Japan. okamotna@takii.kmu.ac.jp
Naofumi
N
Okamoto
Taketoshi
T
Kushida
Kenichi
K
Oe
Masayuki
M
Umeda
Susumu
S
Ikehara
Hirokazu
H
Iida
D000125:Achilles Tendon / Q000293:injuries* / Q000378:metabolism / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D001696:Biomechanical Phenomena; D016026:Bone Marrow Transplantation; D024061:Collagen Type III / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D016059:Range of Motion, Articular; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012421:Rupture / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D013708:Tendon Injuries / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing
D024061:Collagen Type III; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A