Treating Achilles Tendon Rupture in Rats with Bone-Marrow-Cell Transplantation Therapy

Okamoto, Naofumi; Kushida, Taketoshi; Oe, Kenichi; Umeda, Masayuki; Ikehara, Susumu; Iida, Hirokazu
December 2010
Journal of Bone & Joint Surgery, American Volume;12/1/2010, Vol. 92-A Issue 17, p2776
Academic Journal
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/NsIc (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. Clinical Relevance: The present study provides evidence that transplantation of bone marrow cells may be a promising therapy for the treatment of Achilles tendon rupture.


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