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Cell-mediated gene therapy for rotator tendon repair

Authors: M.I. Loebenberg, G. Pelled, A. Hoffman, Y. Zilberman, H. Shinar, K.

References: SECEC 2005

Abstract
AIMS: New biotechnologies create opportunities for gene therapy to assist rotator cuff healing.

MATERIAL: Nonviral methods were utilised to produce genetically engineered Adult Mesenchymal Stem Cells (AMSCs) to up regulate expression of the Smad8 signalling molecule and promote differentiation into tendon like tissues. A previously validated animal model was utilized to examine rotator cuff healing. A 2 mm x 2 mm full thickness defect was created in the Infraspinatus tendon of 8 nude rats. A collagen bio membrane containing engineered cells was sewn into the defect. An identical control procedure was repeated on the contra lateral side with sponges containing non engineered AMSCs.

RESULTS: 4 weeks post implantation, the area of the injection or implantation was isolated and analysed by, light microscopy and histochemical staining. Analysis of the engineered implants (C3H-BMP2-SMAD8 L+MH2) revealed the formation of dense connective tissue with parallel organised fibres and spindle shaped cells, unlike the control samples. Proton Double Quantum Filtered Magnetic Resonance Imaging techniques of the rotator cuff tendons demonstrated an increased presence of organised tendon in the engineered rotator cuff tissues when compared with either native rotator cuff or those treated with non engineered AMSCs.

CONCLUSION: This is the first report showing a particular SMAD signalling cascade involved in the repair of rotator cuff tendon. These findings may have considerable importance for tendon healing and may indicate a clinical gene therapy platform to augment surgical repair.

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