Emerging ideas: Evaluation of stem cells genetically modified with scleraxis to improve rotator cuff healing

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.

Fig. 1

The schematic shows how this technology may be used to augment rotator cuff repairs in the future. MSC = mesenchymal stem cells; RTC - rotator cuff.