BMP-14 Gene Therapy Increases Tendon Tensile Strength in a Rat Model of Achilles Tendon Injury

Bolt, Patrick; Clerk, Avnish Neil; Luu, Hue H.; Kang, Qi; Kummer, Jennifer L.; Deng, Zhong‐Liang; Olson, Kristin; Primus, F. James; Montag, Anthony; He, Tong‐Chuan; Haydon, Rex C.; Toolan, Brian C.

doi:10.2106/00004623-200706000-00021

Cited by 88 publications

(57 citation statements)

References 18 publications

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“…Modified Kessler suturing and VEGF application without plantaris tendon support also showed no differences. Bolt et al (5) showed a positive effect of BMP-14 gene therapy on rat AT injuries, 1-3 weeks after surgery.…”

Section: Discussionmentioning

confidence: 99%

Impact of combinatory growth factor application on rabbit Achilles tendon injury with operative versus conservative treatment: A pilot study

Konerding¹

2009

Int J Mol Med

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Abstract. Acute Achilles tendon (AT) rupture is a common injury with a comparatively high complication rate. Presently, surgical treatments compete with nonoperative treatment modalities. The aim of this study was to elucidate the possible beneficial effects of short-term combinatory application of growth factors on tendon healing during operative or conservative treatment. In this controlled laboratory study, the left ATs of 40 adult New Zealand White rabbits were transected and either sutured or treated conservatively. Half of the animals from each treatment modality group repetitively received a mixture of VEGF165, bFGF, and rPDGF which was administered peritendineally. The left legs were immobilized with external fixateurs for 6 weeks. The ATs were harvested 3 months after intervention. Tensile strength tests revealed no significant differences between operative and conservative treatments. Compared to the normal right ATs, 60% of the average breaking strength was reached 3 months after surgery. Growth factor application did not result in significant improvements. Only a tendency towards higher blood vessel densities was noted in the groups treated with the factors. Collagen type I/III ratios also displayed no significant differences. This study indicates that there is no difference in the biomechanical outcome of conservative versus operative AT rupture treatment and only a marginal impact of short-term combinatory growth and angiogenesis factor application.

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Section: Discussionmentioning

confidence: 99%

Impact of combinatory growth factor application on rabbit Achilles tendon injury with operative versus conservative treatment: A pilot study

Konerding¹

2009

Int J Mol Med

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“…Bolt et al 23 injected an adenovirus carrying BMP-14 at the site of the repaired tendon. With this procedure, a significantly increased tensile strength was apparent at week 2.…”

Section: Discussionmentioning

confidence: 99%

Ex vivo adenoviral transfer of bone morphogenetic protein 12 (BMP-12) cDNA improves Achilles tendon healing in a rat model

et al. 2008

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The aim of our study was to evaluate the histological and biomechanical effects of BMP-12 gene transfer on the healing of rat Achilles tendons using a new approach employing a genetically modified muscle flap. Biopsies of autologous skeletal muscle were transduced with a type-five, first-generation adenovirus carrying the human BMP-12 cDNA (Ad.BMP-12) and surgically implanted around experimentally transected Achilles tendons in a rat model. The effect of gene transfer on healing was evaluated by mechanical and histological testing after 1, 2, 4 and 8 weeks. One week after surgery, the maximum failure load of the healing tendons was significantly increased in the BMP-12 group, compared with the controls, and the tendon stiffness was significantly higher at 1, 2 and 4 weeks. Moreover, the size of the rupture callus was increased in the presence of BMP-12 and there was evidence of accelerated remodeling of the lesion in response to BMP-12. Histological examination showed a much more organized and homogeneous pattern of collagen fibers at all time points in lesions treated with the BMP-12 cDNA muscle graft. Both single fibrils and the collagen fibers had a greater diameter, with a higher degree of collagen crimp than the collagen of the control groups. This was confirmed by sirius red staining in conjunction with polarized light microscopy, which showed a higher shift of small yellow-green fibers to strong yelloworange fibers after 2, 4 and 8 weeks in the presence of BMP-12 cDNA. There was also an earlier shift from fibroblasts to fibrocytes within the healing tendon, with less fat cells present in the tendons of the BMP-12 group compared with the controls. Treatment with BMP-12 cDNA-transduced muscle grafts thus produced a promising acceleration and improvement of tendon healing, particularly influencing early tissue regeneration, leading to quicker recovery and improved biomechanical properties of the Achilles tendon. Further development of this approach could have clinical applications.

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“…24 Further, it was recently reported that GDF-5 gene therapy increased rat Achilles tendon tensile strength, without inducing bone or cartilage formation within the healed tendon. 25 Recent microarray data from our laboratory showed that GDF-5, when used to treat tendon fibroblasts, plays a role in the regulation of genes critical to cell proliferation, inflammation, and ECM production. 26 Other groups from within our laboratory have shown successful osteogenic differentiation of GDF-5-treated ADMSCs in vitro and on a bioengineered scaffold.…”

mentioning

confidence: 99%

Adipose-Derived Mesenchymal Stem Cells Treated with Growth Differentiation Factor-5 Express Tendon-Specific Markers

Park

Hogan

Kesturu

et al. 2010

Tissue Engineering Part A

142

132

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BMP-14 Gene Therapy Increases Tendon Tensile Strength in a Rat Model of Achilles Tendon Injury

Cited by 88 publications

References 18 publications

Impact of combinatory growth factor application on rabbit Achilles tendon injury with operative versus conservative treatment: A pilot study

Impact of combinatory growth factor application on rabbit Achilles tendon injury with operative versus conservative treatment: A pilot study

Ex vivo adenoviral transfer of bone morphogenetic protein 12 (BMP-12) cDNA improves Achilles tendon healing in a rat model

Adipose-Derived Mesenchymal Stem Cells Treated with Growth Differentiation Factor-5 Express Tendon-Specific Markers

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