Adipose-Derived Stromal Vascular Fraction and Cultured Stromal Cells as Trophic Mediators for Tendon Healing.
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.
© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
Publication Date: 2019-04-29 PubMed ID: 30977556DOI: 10.1002/jor.24307Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research explores the use of adipose-derived stromal vascular fraction (SVF) and adipose tissue-derived stromal cells (ASC) in improving tendon healing. It investigates how these cells act as stimulating factors that orchestrate and enhance the tendon healing process.
Understanding the Role of SVF and ASC in Tendon Healing
- The study focuses on the potential of ASC, which are derived from SVF, to act as “trophic mediators” that stimulate tendon healing. SVF is a diverse population of cells obtained from adipose (fat) tissue, which when expanded in culture, yields a uniform population of ASC.
- The researchers obtained these SVF, ASC, and tenocytes (tendon cells) from the superficial flexor tendons and adipose tissue of adult horses. The cells were then used to study gene expression and growth factors, as well as cell migration in chemotaxis assays, which measure the movement of cells in response to chemical stimuli.
The Impact of SVF and ASC on Cell Migration and Growth Factor Concentration
- It was found that the SVF had significantly higher expression of genes for growth factors such as insulin-like growth factor 1 (IGF-1), stromal cell-derived factor-1α (SDF-1α), and transforming growth factor-β1 (TGF-β1) compared to the ASC.
- On the other hand, the concentration of these growth factors was significantly higher in the medium conditioned by ASC, indicating that ASC can augment the production of these growth factors. Specifically, there was a 4-fold increase in IGF-1 and a 6-fold increase in SDF-1α.
- Fascinatingly, the ASC-conditioned medium induced a significant cell migration in a dose-dependent manner, implying a larger number of ASC, the greater the migration of cells.
Enhancement of Tendon Healing through SVF and ASC Co-Culture
- When tenocytes were co-cultured with autologous ASC (sourced from the same individual), there was a modest but significant increase in the expression of genes for collagen, decorin, and oligomeric matrix protein, which are components necessary for tendon repair and function.
- The results validate the capability of SVF and ASC to function as trophic mediators in tendon healing, particularly through chemotaxis, thereby enhancing the intrinsic healing response.
- To confirm these findings and ascertain the full therapeutic potential of SVF and ASC in treating tendon injuries, further in vivo (within the living organism) studies are recommended.
Cite This Article
APA
Polly SS, Nichols AEC, Donnini E, Inman DJ, Scott TJ, Apple SM, Werre SR, Dahlgren LA.
(2019).
Adipose-Derived Stromal Vascular Fraction and Cultured Stromal Cells as Trophic Mediators for Tendon Healing.
J Orthop Res, 37(6), 1429-1439.
https://doi.org/10.1002/jor.24307 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia.
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia.
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia.
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia.
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia.
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia.
- Laboratory for Statistical Design and Study Analysis, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia.
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia.
MeSH Terms
- Adipose Tissue / cytology
- Animals
- 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
- Tendons / physiology
- Transforming Growth Factor beta1 / analysis
- Transforming Growth Factor beta1 / genetics
Grant Funding
- United States Equestrian Federation
- Vet Stem, Inc.
- Veterinary Orthopedic Society
- Merial Veterinary Scholars Program (ED, SMA, TJS summer stipend)
Citations
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