Skubis-Sikora Aleksandra, Sikora Bartosz, Małysiak Weronika, Wieczorek Patrycja, Czekaj Piotr
Department of Cytophysiology, Chair of Histology and Embryology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-055 Katowice, Poland.
Pharmaceuticals (Basel). 2023 Sep 1;16(9):1236. doi: 10.3390/ph16091236.
Melatonin is a hormone secreted mainly by the pineal gland and acts through the Mel1A and Mel1B receptors. Among other actions, melatonin significantly increases osteogenesis during bone regeneration. Human adipose-derived mesenchymal stem cells (ADSCs) are also known to have the potential to differentiate into osteoblast-like cells; however, inefficient culturing due to the loss of properties over time or low cell survival rates on scaffolds is a limitation. Improving the process of ADSC expansion in vitro is crucial for its further successful use in bone regeneration. This study aimed to assess the effect of melatonin on ADSC characteristics, including osteogenicity. We assessed ADSC viability at different melatonin concentrations as well as the effect on its receptor inhibitors (luzindole or 4-P-PDOT). Moreover, we analyzed the ADSC phenotype, apoptosis, cell cycle, and expression of and receptors, and its potential for osteogenic differentiation. We found that ADSCs treated with melatonin at a concentration of 100 µM had a higher viability compared to those treated at higher melatonin concentrations. Melatonin did not change the phenotype of ADSCs or induce apoptosis and it promoted the activity of some osteogenesis-related genes. We concluded that melatonin is safe, non-toxic to normal ADSCs in vitro, and can be used in regenerative medicine at low doses (100 μM) to improve cell viability without negatively affecting the osteogenic potential of these cells.
褪黑素是一种主要由松果体分泌的激素，通过Mel1A和Mel1B受体发挥作用。在其他作用中，褪黑素在骨再生过程中能显著促进成骨作用。人脂肪来源的间充质干细胞（ADSCs）也已知具有分化为成骨样细胞的潜力；然而，由于随着时间推移特性丧失导致的低效培养或在支架上的低细胞存活率是一个限制因素。改善ADSCs体外扩增过程对于其在骨再生中的进一步成功应用至关重要。本研究旨在评估褪黑素对ADSCs特性（包括成骨能力）的影响。我们评估了不同褪黑素浓度下ADSCs的活力以及其受体抑制剂（鲁辛朵或4-P-PDOT）的作用。此外，我们分析了ADSCs的表型、凋亡、细胞周期以及 和 受体的表达，及其成骨分化潜力。我们发现，与用较高浓度褪黑素处理的ADSCs相比，用100 μM浓度褪黑素处理的ADSCs具有更高的活力。褪黑素没有改变ADSCs的表型或诱导凋亡，并且它促进了一些与成骨相关基因的活性。我们得出结论，褪黑素在体外对正常ADSCs是安全、无毒的，并且可以以低剂量（100 μM）用于再生医学，以提高细胞活力而不会对这些细胞的成骨潜力产生负面影响。
