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Neotendon formation induced by manipulation of the Smad8 signalling pathway in mesenchymal stem cells
Andrea Hoffmann, … , Gerhard Gross, Dan Gazit
Andrea Hoffmann, … , Gerhard Gross, Dan Gazit
Published April 3, 2006
Citation Information: J Clin Invest. 2006;116(4):940-952. https://doi.org/10.1172/JCI22689.
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Research Article

Neotendon formation induced by manipulation of the Smad8 signalling pathway in mesenchymal stem cells

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Abstract

Tissue regeneration requires the recruitment of adult stem cells and their differentiation into mature committed cells. In this study we describe what we believe to be a novel approach for tendon regeneration based on a specific signalling molecule, Smad8, which mediates the differentiation of mesenchymal stem cells (MSCs) into tendon-like cells. A biologically active Smad8 variant was transfected into an MSC line that coexpressed the osteogenic gene bone morphogenetic protein 2 (BMP2). The engineered cells demonstrated the morphological characteristics and gene expression profile of tendon cells both in vitro and in vivo. In addition, following implantation in an Achilles tendon partial defect, the engineered cells were capable of inducing tendon regeneration demonstrated by double quantum filtered MRI. The results indicate what we believe to be a novel mechanism in which Smad8 inhibits the osteogenic pathway in MSCs known to be induced by BMP2 while promoting tendon differentiation. These findings may have considerable importance for the therapeutic replacement of tendons or ligaments and for engineering other tissues in which BMP plays a pivotal developmental role.

Authors

Andrea Hoffmann, Gadi Pelled, Gadi Turgeman, Peter Eberle, Yoram Zilberman, Hadassah Shinar, Keren Keinan-Adamsky, Andreas Winkel, Sandra Shahab, Gil Navon, Gerhard Gross, Dan Gazit

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Figure 10

Tendon-defect repair demonstrated by micro-MRI.

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Tendon-defect repair demonstrated by micro-MRI.
(A, C, E, G, and I) MSME...
(A, C, E, G, and I) MSME axial sections of Achilles tendon of a rat. (B, D, F, H, and J) DQF images of the same axial sections. Tendon was either implanted with collagen sponge without cells (A and B), left intact (C and D), or implanted with C3H10T1/2-BMP2/Smad8 L+MH2 cells (E and F), C3H10T1/2-BMP2 cells (G and H), or C3H10T1/2-Smad8 L+MH2 cells (I and J). DQF images showed ordered collagen fiber formation in the defect site implanted with C3H10T1/2-BMP2/Smad8 L+MH2 cells at a higher level than that found in the contralateral tendon or in the other experimental groups. Arrows indicate the Achilles tendon at the site of implantation. Circles highlight the DQF signal at the site of implantation or, in the case of no treatment, at the tendon.

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