Effects of Hydrogen Sulfide Donor NaHS on Porcine Vascular Wall-Mesenchymal Stem Cells

• Published in: International journal of molecular sciences Vol. 21; no. 15; p. 5267
• Main Authors: Bernardini, Chiara, La Mantia, Debora, Nesci, Salvatore, Salaroli, Roberta, Algieri, Cristina, Pagliarani, Alessandra, Zannoni, Augusta, Forni, Monica
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.07.2020; MDPI
• Subjects: Angiogenesis; Animals; Antigens, Differentiation - metabolism; Attitudes; Blood Vessels - cytology; Blood Vessels - metabolism; Cardiovascular disease; Cell culture; Cell cycle; Cell viability; Coagulation factors; Coronary vessels; Deoxyribonucleic acid; DNA; Drug dosages; Endothelial Cells - cytology; Endothelial Cells - metabolism; Fibroblasts; gas transmitter; Gene expression; H2S; H2S donors; Hydrogen sulfide; Investigations; Long-term effects; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Morphology; Neovascularization, Physiologic - drug effects; Nestin; Oxidative stress; Physiology; pig model; Reactive Oxygen Species - metabolism; S phase; Stem cell transplantation; Stem cells; Sulfides - pharmacology; Swine; Toxicity; vascular wall–mesenchymal stem cells; H2S; H2S donors, vascular wall–mesenchymal stem cells, pig model; gas transmitter
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21155267

Hydrogen sulfide (H S) is now considered not only for its toxicity, but also as an endogenously produced gas transmitter with multiple physiological roles, also in maintaining and regulating stem cell physiology. In the present work, we evaluated the effect of a common H S donor, NaHS, on porcine vascular wall-mesenchymal stem cells (pVW-MSCs). pVW-MSCs were treated for 24 h with increasing doses of NaHS, and the cell viability, cell cycle, and reactive oxygen species (ROS) production were evaluated. Moreover, the long-term effects of NaHS administration on the noteworthy characteristics of pVW-MSCs were analyzed. The MTT test revealed no alteration in cell viability, however, the cell cycle analysis demonstrated that the highest NaHS dose tested (300 μM) determined a block in S phase, which did not depend on the ROS production. Moreover, NaHS (10 μM), continuously administered in culture for 21 days, was able to significantly reduce NG2, Nestin and PDGFR-β expression. The pro-angiogenic attitude of pVW-MSCs was partially reduced by NaHS: the cells maintained the ability to grow in spheroid and sprouting from that, but endothelial markers (Factor VIII and CD31) were reduced. In conclusion, NaHS can be toxic for pVW-MSCs in high doses, while in low doses, it influences cellular physiology, by affecting the gene expression with a slowing down of the endothelial lineage.