Department of Immunology, Yeditepe University Faculty of Medicine, İstanbul, Turkey
Department of Medical Biology, Yeditepe University Faculty of Medicine, İstanbul, Turkey
Balkan Med J. 2023 Mar 8;40(2):117-123. doi: 10.4274/balkanmedj.galenos.2022.2022-10-21. Epub 2023 Feb 7.
Various studies have reported the effects of testosterone on different cell types, yet bone marrow-derived mesenchymal stem cells’ cellular responses to testosterone remain unknown.
To investigate the effects of testosterone propionate, an oil-soluble short-acting form of testosterone, on human bone marrow-derived mesenchymal stem cells’ proliferation and viability after 24 hours of incubation. We also investigated the impact of testosterone propionate on bone marrow-derived mesenchymal stem cell’s polarization and cytotoxicity on K562 leukemia cell line.
In vitro study.
We expanded commercially available bone marrow derived mesenchymal stem cells in vitro and treated them with testosterone propionate at concentrations ranging from 10-10 M for 24 hours. Ideal concentration was determined by evaluating cellular viability and proliferation with Annexin V/Propidium Iodide assay and carboxyfluorescein succinimidyl ester staining. The characteristic features of bone marrow-derived mesenchymal stem cells were evaluated by immunophenotyping and investigating their differentiation capacities. Bone marrow-derived mesenchymal stem cells’ cytotoxic properties upon testosterone propionate treatment were determined by co-culturing the cells with K562 cells and with confocal imaging investigating polarization.
Testosterone propionate promoted proliferation and maintained the viability of bone marrow-derived mesenchymal stem at 10 M concentration. Further evaluations were conducted with the determined dose. The results showed that, apart from promoting mesenchymal stem cells’ polarization and increasing their cytotoxicity on K562 cells, testosterone propionate did not alter differentiation capacities of bone marrow-derived mesenchymal stem cells and certain cell surface markers, but led to a significant increase in HLA-DR expression.
The findings reveal that testosterone propionate promotes the proliferation and survival of bone marrow-derived mesenchymal stem cells in a dose-dependent manner without hampering their differentiation capacities, induces their polarization to the pro-inflammatory phenotype, and increases their cytotoxicity on the K562 cell line.
多项研究报道了睾酮对不同细胞类型的影响,但骨髓间充质干细胞对睾酮的细胞反应仍不清楚。
研究睾酮丙酸酯(睾酮的一种油溶性短效形式)在孵育 24 小时后对人骨髓间充质干细胞增殖和活力的影响。我们还研究了睾酮丙酸酯对骨髓间充质干细胞向促炎表型极化的影响及其对 K562 白血病细胞系的细胞毒性。
体外研究。
我们在体外扩增市售的骨髓间充质干细胞,并在 10-10 M 浓度范围内用睾酮丙酸酯处理它们 24 小时。通过用 Annexin V/碘化丙啶检测和羧基荧光素琥珀酰亚胺酯染色评估细胞活力和增殖来确定理想浓度。通过免疫表型评估和研究其分化能力来评估骨髓间充质干细胞的特征。通过与 K562 细胞共培养并用共聚焦成像研究极化来确定睾酮丙酸酯处理后骨髓间充质干细胞的细胞毒性特性。
睾酮丙酸酯在 10 M 浓度下促进增殖并维持骨髓间充质干细胞的活力。在确定的剂量下进行了进一步的评估。结果表明,除了促进间充质干细胞的极化和增加其对 K562 细胞的细胞毒性外,睾酮丙酸酯不会改变骨髓间充质干细胞的分化能力和某些细胞表面标志物,但会导致 HLA-DR 表达显著增加。
研究结果表明,睾酮丙酸酯以剂量依赖的方式促进骨髓间充质干细胞的增殖和存活,而不会损害其分化能力,诱导其向促炎表型极化,并增加其对 K562 细胞系的细胞毒性。