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

Chiara Bernardini,Monica Forni,Roberta Salaroli,Salvatore Nesci,Debora La Mantia,Augusta Zannoni,Cristina Algieri,Alessandra Pagliarani

doi:10.3390/ijms21155267

Chiara Bernardini, Monica Forni + Show 6 more

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https://doi.org/10.3390/ijms21155267

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Abstract

Hydrogen sulfide (H2S) 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 H2S 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.

Highlights

Hydrogen sulfide (H2S) has long been known for its toxicity, it is well documented as a endogenously produced gas transmitter, which would act as a cell modulator as nitric oxide (NO) and carbon monoxide (CO) [1,2,3,4].In order to cast light on the physiological H2S properties, many different inhibitors of H2S synthesis or exogenous donors have been used
Recent interest has been addressed to the role of H2S in the field of mesenchymal stem cells (MSCs), so the use of H2S donors has been proposed to treat various pathological situations such as osteoporosis, immune disorders, inflammation and cardiovascular disease [17,18,19,20,21]
We investigated the effects of a well known H2S donor, NaHS, on vascular stem cells isolated from the porcine thoracic aorta

Summary

Introduction

In order to cast light on the physiological H2S properties, many different inhibitors of H2S synthesis or exogenous donors have been used. Among these donors, NaHS and Na2S were often used in in vitro studies, [5]. At physiological pHs, the S2- concentration is insignificant, but H2S and HS- coexist in a proportion which varies according to the different ambient conditions. Since the two species can activate different signaling pathways [7], the same nominal H2S concentration can lead to different effects in different cells. The toxicity of H2S donors seems to be due to a DNA-damaging mutagen property [11], as demonstrated in glioblastoma (GBM) cells, where NaHS interferes with cell cycle phases. The genotoxic effects could involve autoxidation mechanisms that generate reactive oxygen species (ROS) radicals [11,12] or mechanisms that impair DNA repairing via post-translational sulfhydration [13]

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