Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of the Romanian Academy, Bucharest, Romania.
Infection and Immunity Laboratory, National Institute for Research and Development in Microbiology and Immunology 'I. Cantacuzino', Bucharest, Romania.
J Mol Endocrinol. 2018 Jan;60(1):1-15. doi: 10.1530/JME-17-0185.
The use of mesenchymal stem cells (MSC) as a therapeutic tool in cardiovascular diseases is promising. Since androgens exert some beneficial actions on the cardiovascular system, we tested our hypothesis that this hormone could promote MSC-mediated repair processes, also. Cultured MSCs isolated from Wharton's jelly were exposed to 30 nM dihydrotestosterone (DHT) for 1 or 4 days and the effects of the hormone on their growth/migration/adhesion and the underlying mechanisms were assessed. Results were obtained by real-time cell impedance measurements, and DNA quantification showed that DHT increased MSC proliferation by 30%. As determined by xCELLigence system, DHT augmented (2 folds) the migration of MSC toward cardiac tissue slices (at 12 h), and this effect was blocked by flutamide, an androgen receptor (AR) antagonist. Exposure of cells to DHT, upregulated the gene and protein expression of , and and downregulated the expression of DHT significantly induced the release of nitric oxide by MSC (≥2-fold) and flutamide blocked this effect. When MSCs were co-cultured with cardiac slices, immunohistochemical analysis and qRT-PCR showed that the integration of DHT-stimulated MSC was significantly higher than that of in controls. In conclusion, our findings provide the first evidence that DHT promotes MSC growth, migration and integration into the cardiac slices. The modulating effects of DHT were associated with upregulation of ARs and of key molecules known to promote tissue remodeling and angiogenesis. Our findings suggest that priming of MSC with DHT may potentially increase their capability to regenerate cardiac tissue; studies are needed to confirm our findings.
间质干细胞（MSC）作为一种治疗心血管疾病的工具具有广阔的应用前景。由于雄激素对心血管系统有一定的有益作用，我们验证了我们的假设，即这种激素也可以促进 MSC 介导的修复过程。我们从 Wharton 胶中分离出 MSC 进行培养，并用 30 nM 的二氢睾酮（DHT）处理 1 天或 4 天，评估激素对其生长/迁移/黏附的影响及其潜在机制。结果通过实时细胞阻抗测量获得，DNA 定量显示 DHT 使 MSC 增殖增加了约 30%。通过 xCELLigence 系统确定，DHT 增强了 MSC 向心脏组织切片迁移的能力（在 12 小时），而这种作用被雄激素受体（AR）拮抗剂氟他胺阻断。DHT 使细胞暴露，上调 、 、 和 基因和蛋白的表达，并下调 的表达。DHT 显著诱导 MSC 释放一氧化氮（≥2 倍），而氟他胺阻断了这种作用。当 MSC 与心脏切片共培养时，免疫组织化学分析和 qRT-PCR 显示，DHT 刺激的 MSC 整合明显高于对照组。总之，我们的研究结果首次证明 DHT 促进 MSC 的生长、迁移和整合到心脏切片中。DHT 的调节作用与 AR 及其已知促进组织重塑和血管生成的关键分子的上调有关。我们的研究结果表明，用 DHT 预处理 MSC 可能会增加其再生心脏组织的能力；需要进一步的研究来证实我们的发现。
