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Novel Approach to Treat Rotator Cuff Tear Using Tendon Stem/Progenitor Cell (TSC) Sheets
Issei Komatsu, MD; Yaron Sela, MD; Kevin Kruse, MD; James HC. Wang, MD; Christopher C. Schmidt, MD; Mark E. Baratz, MD
University of Pittsburgh, Pittsburgh, PA

Introduction: Rotator cuff tear is a highly prevalent clinical problem. The healing tendon tissue recovers poorly and does not have the same biochemical and mechanical properties of an uninjured tendon because of scar formation and ossification. Therefore, there is an urgent need to discover new treatment measures to effectively improve the rate and quality of healing cuff tendons. Here, we established a chronic rabbit rotator cuff tear model and used novel tendon stem/progenitor cell (TSC) sheets to enhance tendon healing.

Methods: TSCs were isolated from rabbit biceps tendons and cell sheets were prepared by plating 1.5x105 TSCs on temperature-responsive culture dishes (UpCellTM, Cell Seed Inc. Tokyo, Japan). A total of 40 rabbits underwent the supraspinatus tendon detachment surgery (Figure 1e) and then were randomly allocated to 2 groups: repair and repair + implantation of autologous TSC sheet. Six weeks after the detachment, torn tendons were repaired using suture anchors (Figure 1f). In TSC sheet group, TSC sheet was grafted at the site of repair (Figure 1g). At 4 and 8 weeks after the repair surgeries, we perform histological and immunohistochemical evaluation, and biomechanical testing of the repaired tendons.

Results: Rabbit TSCs were successfully isolated from biceps tendons (Figure 1a) and showed stem cell features. The TSCs sheets were successfully produced as a transplantable monolayer sheet form using temperature-sensitive culture dish (Figure 1b,1c and 1d). Next, in vivo histology and immunohistochemistry examinations demonstrated that the cell sheet was observed on surface of footprint at tendon-bone junction 8 weeks after implantation (Figure 1h and 1i). Tissue at tendon-bone junction in TSC sheet group appeared thicker and well organized, and there were elongated spindle shape cells. In contrast, relatively thinner tissue and disorganized cellular arrangement were observed in control. Biomechanical testing of the repaired supraspinatus tendons is currently underway.

Discussion: This study represents the first efforts to systemically evaluate the role of TSCs in the form of sheet implantation in the healing of injured rotator cuff tendon in a rabbit model. Since TSC sheet stayed on the footprint surface it is likely that transplantation of a monolayer sheet of TSCs with collagen rich extracellular matrix at the site of rotator cuff tear would accelerate tendon-bone healing. The use of TSC sheets may eliminate the need of synthetic scaffolds for cell delivery, which may not be biocompatible and biodegradable, but be immunogenic.

Figure 1

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