Pro-regenerative effects of 5-hydroxytryptamine in cultured dermal fibroblasts and subcutaneous adipose tissue-derived mesenchymal stromal cells

BACKGROUND: Mesenchymal stem cells of the skin and subcutaneous adipose tissue play a critical role in epithelial regeneration by proliferating and differentiating into skin cells to replace damaged or dead tissue. In addition, they act via autocrine and paracrine signaling to promote tissue repair and wound healing. AIM: The work aimed to investigate the in vitro effects of serotonin on the regenerative potential—namely, proliferation, migration, and cell death—of dermal fibroblasts (DFs) and subcutaneous adipose tissue-derived mesenchymal stromal cells (SAT-MSCs). METHODS: Primary DF and SAT-MSC cultures were obtained from Wistar rats and divided into the following groups: DF/SAT-MSCs cultured in standard medium and DF/SAT-MSCs cultured with serotonin supplementation. Cell morphology and proliferation were assessed microscopically using an Axio Vert.A1 microscope (Carl Zeiss, Germany). Cell migration dynamics were studied in a scratch assay. Cell death resulting from apoptosis and/or necrosis was evaluated using fluorescence microscopy with Annexin V-FITC/PI staining (ServiceBio, China). RESULTS: Both DFs and SAT-MSCs responded to serotonin supplementation in standard culture medium with increased proliferation. Quantification of migrated cells revealed an increase in the conditional migration speed of SAT-MSCs under conditions of serotonin supplementation. Additionally, serotonin-treated cultures demonstrated reduced levels of apoptotic and necrotic cells. CONCLUSION: Activation of serotonin signaling mechanisms plays an important role in wound healing following various skin and subcutaneous tissue injuries by enhancing cell viability, DF proliferation, and both proliferation and migration of SAT-MSCs, as demonstrated in our study. These findings suggest that serotonin or 5-hydroxytryptamine receptor agonists may serve as promising candidates for promoting skin repair in patients with injuries. Importantly, the cellular response to serotonin signaling is tissue-specific and depends on the receptor subtype and intracellular signaling pathways mediating secondary messenger activation.