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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 Article has an altmetric score of 3

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 7

Achilles tendon regeneration model.

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Achilles tendon regeneration model.
An Achilles tendon partial-thicknes...
An Achilles tendon partial-thickness defect was created in athymic rats. Adult athymic rats (4 months old) were anesthetized as described in Methods. The Achilles tendon (indicated by arrow) was separated from the plantaris and soleus tendons (A), and a 3-mm partial-resection defect was created in its lateral substance (B, arrows indicate the span of the defect). Cells (3 × 106) were seeded onto a collagen sponge (arrow), which was then placed within the tendon defect and sutured to the tendon (C). The skin was closed in a routine manner using 2-0 Mersilk. (D) Noninvasive monitoring of cell survival in the implantation site. C3H10T1/2-BMP2/Smad8 L+MH2 progenitor cells expressing the luciferase gene were implanted in an Achilles tendon defect in the rat. CCCD analysis demonstrated a positive luciferase signal detected in the implantation site (arrow), indicating the survival of implanted cls.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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Referenced in 3 patents
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