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Emerging Ideas: Evaluation of Stem Cells Genetically Modified with Scleraxis to Improve Rotator Cuff Healing

  • Emerging Ideas
  • Published:
Clinical Orthopaedics and Related Research®

Abstract

Background

Rotator cuffs heal with an interposed layer of scar tissue that makes repairs prone to failure. Cell-based biologic therapies have the potential to augment this healing process. Scleraxis (Scx) is a transcription factor that is involved in tendon development during embryogenesis, and may help drive stem cells toward tenocyte differentiation in adults.

Questions/Hypothesis

(1) Overexpression of Scx with adenoviral-mediated gene transfer in stem cells will drive pluripotent stem cells toward tenoblastogenic lineages in vitro; (2) the application of these genetically modified cells will result in improved histologic and biomechanical healing of rotator cuff repairs.

Method of study

For the first hypothesis, we will determine whether stem cells derived from various sources can differentiate into tenocytes when genetically modified with Scx in vitro. We will assess morphologic features of cells with light microscopy, and gene expression analyses to confirm phenotypes consistent with tenocyte differentiation. For the second hypothesis, we will determine whether these genetically modified cells augment rotator cuff repairs in a rat model based on histology and biomechanical outcomes.

Significance

Development of this technology may substantially advance our ability to repair large to massive rotator cuff tears while limiting the rates of anatomic failure.

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Acknowledgments

We thank the following people for input in this study design: Chisa Hidaka MD, Christina Cheng BS, Matthew Cunningham MD, PhD, and Steven Swendeman PhD. We also thank Ronen Schweitzer PhD, for generously supplying the mouse Scx cDNA.

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Authors and Affiliations

  1. Sports Medicine/Shoulder Service, Hospital for Special Surgery, New York, NY, USA

    Lawrence V. Gulotta MD & Scott A. Rodeo MD

  2. Hospital for Special Surgery, 535 E 70th Street, New York, NY, 10021, USA

    Lawrence V. Gulotta MD

Authors
  1. Lawrence V. Gulotta MD
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  2. Scott A. Rodeo MD
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Corresponding author

Correspondence to Lawrence V. Gulotta MD.

Additional information

Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.

Each author certifies that his or her institution approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

This work was performed at the Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, NY, USA.

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Gulotta, L.V., Rodeo, S.A. Emerging Ideas: Evaluation of Stem Cells Genetically Modified with Scleraxis to Improve Rotator Cuff Healing. Clin Orthop Relat Res 469, 2977–2980 (2011). https://doi.org/10.1007/s11999-010-1727-4

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  • DOI: https://doi.org/10.1007/s11999-010-1727-4

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