Umbilical cord mesenchymal stem cells effect on melanoma progression

• Autor(a) principal: Fernandes, Pablo Rende
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.22/24773
• topic: Melanoma; hUCMSCs; CM; Secretome; B16F10 cells; Accelular therapy

Melanoma, a skin cancer originating from malignant transformation of melanocytes, is charcaterized by its agressive nature and high tendency to metastasize, rendering melanoma management challenging. The few existing treatments for metastatic melanoma have limited effectiveness, underlying a demand for novel therapeutic strategies. In preclinical cancer models, huma umbilical cord mesenchymal stem cells (huCMSCs) have show promising anti-cancer effects, hampering both the proliferation and metastasis of malignant cells. In this work, we investigated the impacto f conditioned media (CM) obtained from huCMSCs on viability, proliferation, cell cycle, migration, and ahesion of melanoma cells using in vitro cell culture models. huCMSCs, isolated from the umbilical cordo f seven healthy neonates by enzymatic digestion followed by direct plastic adherance method, were cultivated and their CM stored for subsequente assays. Then, malignant melanoma B16F10 cells were treated with final concentration of 100% of CM or standard sérum-free media (control)for 24 hours. Cell viability was assessed using MTT assay and 7-aminoactinomycin D (7-ADD) staining assay. When treated wich huCMSCs secretome, B16F10 cells decreased their viability by 32% and 11% as shown by the MTT assay and 7-AAD exclusion stain, respectively (p˂0.05, n=7). Next proliferation and cell cycle progression were evaluated by flow cytometry analysis with Ki-67 and propidium iodide (PI) stains, respectively. The expression of Ki-67 proliferation marker was reduced by 14% (p˂0.05, n=7) with a concomitante increase in the number of cells in G0/G1 phase arrest (6%). huCMSCs-CM reuced cell migration, assessed by scratch assay, by 24% (p˂0.05 vs control, n=7) while enhancing cell adhesion capacity, evaluated bgy the crystal violet assay, by 16% (p˂0.05 vs control, n=7). Our results showed that huCMSCs secretome reduced the viability and proliferation capacity of malignant melanoma cells with a concomitante arresto f cells in G0/G1 cell cycle stage. This study suggests huCMSCs paracrine signaling induces melanoma cells into a quiescente growth inhibition state with a concomitante decrease in overall cell viability and survial. Further research is required to characterize the molecular pathways of these promising effects of huCMSCs secretome in inhibiting melanoma cells porliferation and establish their safety and efficacy. Altogether, our findings support huCMSCs paracrine componente therapies for melanoma.