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.
J Orthop Res. 2019 Jun;37(6):1429-1439. doi: 10.1002/jor.24307. Epub 2019 Apr 29.
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.
脂肪组织来源的基质血管部分（SVF）是一种异质细胞群体，当培养扩增时，可产生同质的塑料贴附脂肪组织来源的基质细胞（ASC）。SVF 和 ASC 已在临床上用于改善腱愈合，但它们的作用机制尚未完全阐明。本研究的目的是研究 ASC 作为腱愈合营养介质的潜力。从成年马中收获屈肌腱和脂肪组织，以获得 SVF、ASC 和腱细胞。在连续传代中定量测定 SVF 和 ASC 中的生长因子基因表达，并定量测定 ASC 条件培养基（CM）中的生长因子。使用 ASC-CM 进行微趋化分析。将自体 ASC 或同种异体 SVF 与腱细胞共培养。与 ASC 相比，SVF 中的胰岛素样生长因子 1（IGF-1）、基质细胞衍生因子 1α（SDF-1α）、转化生长因子-β1（TGF-β1）和 TGF-β3 的基因表达显著更高。与对照相比，ASC-CM 中的 IGF-1（4 倍）和 SDF-1α（6 倍）浓度显著增加。ASC 条件培养基以剂量依赖性方式诱导显著的细胞迁移。与自体 ASC 共培养后，腱细胞中 I 型和 III 型胶原、饰胶蛋白和软骨寡聚基质蛋白的基因表达适度但显著增加。我们的研究结果支持 SVF 和 ASC 作为腱愈合中的营养介质的能力，特别是通过趋化作用，这对固有愈合反应具有重要影响。需要进行体内研究以进一步阐明 SVF 和/或 ASC 改善腱愈合的潜力。版权所有 © 2019 矫形研究协会。由 Wiley Periodicals, Inc. 出版。J Orthop Res 37:1429-1439, 2019.
