Human Subacromial Bursal Cells Display Superior Engraftment Versus Bone Marrow Stromal Cells in Murine Tendon Repair

Abstract

Background: Bone marrow aspirate is a primary source for cell-based therapies with increasing value in the world of orthopaedic surgery, especially in revision cases of tendon and ligament repairs. However, cells within peritendinous structures, such as the paratenon and surrounding bursa, contribute to the native tendon-healing response and offer promising cell populations for cell-based repair strategies. Therefore, the purpose of this study is to investigate the efficacy of cells derived from human subacromial bursa as compared with the current gold standard, bone marrow stromal cells (BMSCs), for tendon repairs in an established in vivo immunodeficient murine patellar tendon defect model. Hypothesis: Subacromial bursal cells will show superior survival and engraftment into the host tissue as compared with BMSCs. Study Design: Controlled laboratory study. Methods: Human subacromial bursal and bone marrow aspirate were harvested from the same donor undergoing rotator cuff repair. Cells were transfected with a fluorescent lentiviral vector to permanently label the cells, encapsulated into fibrin gel, and implanted into bilateral full-length central-width patellar tendon defects of immunodeficient mice. Additional surgery was performed on control mice comparing fibrin without cells and natural healing. At the time of sacrifice, all limbs were scanned on a multiphoton microscope to monitor the engraftment of the human donor cells. Afterward, limbs were assigned to either immunohistochemical or biomechanical analysis. Results: As compared with BMSCs, implanted subacromial bursal cells displayed superior tissue engraftment and survival. The main healing response in this defect model was the creation of new healing tissue over the anterior surface of the defect space. The implantation of cells significantly increased the thickness of the anterior healing tissue as compared with control limbs that did not receive cells. Cell proliferation was also increased in limbs that received implanted cells, suggesting that the donor cells stimulated a more robust healing response. Finally, these changes in the healing response did not lead to significant changes in mechanical properties. Conclusion: The subacromial bursa, while often removed during rotator cuff repair, may harbor a more suitable cell source for tendon repair than BMSCs, as bursal cells display superior engraftment and survival in tendon tissue. In addition, the subacromial bursa may be a more accessible cell source than bone marrow aspirate. Clinical Relevance: The subacromial bursa contains a cell population that responds to tendon injury and may provide a more optimal cell source for tendon repair and regeneration strategies. Therefore, cells could be harvested from this tissue in the future, as opposed to the current practice of bursectomy and debridement.

Concentrated Bone Marrow Aspirate and Subacromial Bursa-Derived Cells Demonstrate Similar Cellular Adhesion and Proliferation Potential on Demineralized Bone Matrix Scaffolds for Biologic Augmentation of Rotator Cuff Repair

“…Besides, recent studies suggest subacromial bursa to be a potential, easily accessible source for MSCs that can be used for biologic augmentation of rotator cuff repairs, as they fulfil all required characteristics including multilineage differentiation (9-11). Moreover, Dyrna et al found that human SBDCs demonstrated superior tissue engraftment and survival in an animal tendon model when compared to bMSCs (27). The present study found that SBDCs also adhere and proliferate on DBM scaffolds, highlighting their potential as an easily accessible biologic augment in combination with scaffolds to keep the cells at the targeted zone.…”

Analysis of Time to Form Colony Units for Connective Tissue Progenitor Cells (Stem Cells) Harvested From Concentrated Bone Marrow Aspirate and Subacromial Bursa Tissue in Patients Undergoing Rotator Cuff Repair

“…Studies have demonstrated that the paratenon may be instrumental in patella tendon healing. 27 , 28 , 29 The authors feel that the subacromial bursa may serve a similar role in rotator cuff regeneration despite being an extrinsic tissue, perhaps accounting for the large presence of CTPs.…”

“…Previous work by Dyrna et al. 28 has contributed that bursal donated cells may have superior engraftment and survival in healing tendon than cBMA-derived cells. The results of this study further confirm that bursa is capable of forming colony units in culture.…”

Editorial Commentary: Are We Ready to Apply Stem Cell Therapy in Rotator Cuff Tear Surgery?

“…Application of mesenchymal stem cells (MSCs) is one of the promising new options for rotator cuff tear surgery; several articles have shown the positive effects of this augmentation in animal and human studies. [4][5][6][7] All prior studies have used enzymatic digestion with collagenase to isolate MSCs. The current article "Comparison of Preparation Techniques for Isolating Subacromial Bursa-Derived Cells as a Potential Augment for Rotator Cuff Tear" reported by Morikawa, Muench, Baldino, Kia, Johnson, Otto, Pauzenberger, Dyrna, McCarthy, and Mazzocca 8 revealed that a similar number of subacromial bursaederived cells were obtained using a chopping technique to mechanically isolate cells as when using collagenase digestion.…”