Adipose‐Derived Stromal Vascular Fraction and Cultured Stromal Cells as Trophic Mediators for Tendon Healing

• Published in: Journal of orthopaedic research 2019-06, Vol.37 (6), p.1429-1439
• Main Authors: Polly, Shelley S., Nichols, Anne E. C., Donnini, Elle, Inman, Daniel J., Scott, Timothy J., Apple, Stephanie M., Werre, Stephen R., Dahlgren, Linda A.
• Format: Article
• Language: English
• Subjects: Adipose Tissue - cytology; adipose‐derived multipotent cells; Animals; cell biology; Cells, Cultured; Chemokine CXCL12 - analysis; Chemokine CXCL12 - genetics; Coculture Techniques; Horses; Insulin-Like Growth Factor I - analysis; Insulin-Like Growth Factor I - genetics; Stromal Cells - physiology; stromal vascular fraction; tendon/ligament; tendon/ligament, progenitors and stem cells; tendon/ligament, repair and tissue engineering; Tendons - physiology; Transforming Growth Factor beta1 - analysis; Transforming Growth Factor beta1 - genetics
• ISSN: 0736-0266; 1554-527X
• DOI: 10.1002/jor.24307

ABSTRACT Adipose‐derived stromal vascular fraction (SVF) is a heterogeneous population of cells that yields a homogeneous population of plastic‐adherent adipose tissue‐derived stromal cells (ASC) when culture‐expanded. SVF and ASC have been used clinically to improve tendon healing, yet their mechanism of action is not fully elucidated. The objective of this study was to investigate the potential for ASC to act as trophic mediators for tendon healing. Flexor digitorum superficialis tendons and adipose tissue were harvested from adult horses to obtain SVF, ASC, and tenocytes. Growth factor gene expression was quantified in SVF and ASC in serial passages and growth factors were quantified in ASC‐conditioned medium (CM). Microchemotaxis assays were performed using ASC‐CM. Tenocytes were grown in co‐culture with autologous ASC or allogeneic SVF. Gene expression for insulin‐like growth factor 1 (IGF‐1), stromal cell‐derived factor‐1α (SDF‐1α), transforming growth factor‐β1 (TGF‐β1) and TGF‐β3 was significantly higher in SVF compared to ASC. Concentrations were significantly increased in ASC‐CM compared to controls for IGF‐1 (4‐fold) and SDF‐1α (6‐fold). Medium conditioned by ASC induced significant cell migration in a dose‐dependent manner. Gene expression for collagen types I and III, decorin, and cartilage oligomeric matrix protein was modestly, but significantly increased following co‐culture of tenocytes with autologous ASC. Our findings support the ability of SVF and ASC to act as trophic mediators in tendon healing, particularly through chemotaxis, which stands to critically impact the intrinsic healing response. In vivo studies to further delineate the potential for SVF and/or ASC to improve tendon healing are warranted. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1429–1439, 2019.