Orthopaedic Research Laboratory, Department of Orthopaedic Surgery and Traumatology, Odense University Hospital, Department of Clinical Research, University of Southern Denmark, Sdr. Boulevard 29, Odense C, DK-5000, Denmark.
Molecular Endocrinology Laboratory (KMEB), Department of Endocrinology and Metabolism, Odense University Hospital, University of Southern Denmark, J. B. Winsløws Vej 25.1, Odense C, DK-5000, Denmark.
J Biomed Mater Res A. 2017 Dec;105(12):3326-3332. doi: 10.1002/jbm.a.36195. Epub 2017 Sep 19.
Insufficient blood supply may limit bone regeneration in bone defects. Vascular endothelial growth factor (VEGF) promotes angiogenesis by increasing endothelial migration. This outcome, however, could depend on time of application. Sheep mesenchymal stem cells (MSCs) in severe combined immunodeficient (SCID) mice were used in this study to evaluate optimal time points for VEGF stimulation to increase bone formation.
Twenty-eight SCID (NOD.CB17-Prkdc /J) mice had hydroxyapatite granules seeded with 5 × 10 MSCs inserted subcutaneous. Pellets released VEGF on days 1-7, days 1-14, days 1-21, days 1-42, days 7-14, and days 21-42. After 8 weeks, the implant-bone-blocks were harvested, paraffin embedded, sectioned, and stained with both hematoxylin and eosin (HE) and immunohistochemistry for human vimentin (hVim) staining. Blood samples were collected for determination of bone-related biomarkers in serum.
The groups with 5 × 10 MSCs and VEGF stimulation on days 1-14 and days 1-21 showed more bone formation when compared to the control group of 5 × 10 MSCs alone (p < 0.01). Serum biomarkers had no significant values. The hVim staining confirmed the ovine origin of the observed ectopic bone formation.
Optimal bone formation of MSCs was reached when stimulating with VEGF during the first 14 or 21 days after surgery. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3326-3332, 2017.
骨缺损处的血供不足可能会限制骨再生。血管内皮生长因子（VEGF）通过增加内皮细胞迁移来促进血管生成。然而，这种结果可能取决于应用的时间。本研究使用绵羊间充质干细胞（MSCs）在严重联合免疫缺陷（SCID）小鼠中，评估 VEGF 刺激以增加骨形成的最佳时间点。
28 只 SCID（NOD.CB17-Prkdc / J）小鼠将载有 5×10 MSCs 的羟基磷灰石颗粒植入皮下。颗粒在第 1-7 天、第 1-14 天、第 1-21 天、第 1-42 天、第 7-14 天和第 21-42 天释放 VEGF。8 周后，收获植入物-骨块，石蜡包埋，切片，并用苏木精和伊红（HE）以及免疫组织化学染色法对人波形蛋白（hVim）染色进行染色。收集血液样本以测定血清中与骨相关的生物标志物。
与单独使用 5×10 MSCs 的对照组相比，第 1-14 天和第 1-21 天接受 5×10 MSCs 和 VEGF 刺激的组显示出更多的骨形成（p<0.01）。血清生物标志物没有显著值。hVim 染色证实了观察到的异位骨形成的羊源。
在手术后的前 14 或 21 天内用 VEGF 刺激可达到 MSC 的最佳骨形成。© 2017 Wiley Periodicals, Inc. J 生物材料 Res 部分 A：105A：3326-3332，2017。
