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Título/Title/Titulo

Effect of Hepatitis C drugs sofosbuvir and daclatasvir treatment on mesenchymal stem cells viability, autophagy and migration capacity

Introdução/Introduction/Introdución

Mesenchymal stem cells (MSCs) are plastic-aderent, fibroblast-like multipotent adult cells that can differentiate into all cells of mesodermal origin. Recently, several research groups reported MSCs immunoregulatory properties, thus showing potential clinical application in treating immune-based disorders and chronic inflammation. Hepatitis C is characterized by chronic inflammation in the liver, who often leads to fibrosis, cirrhosis, and death. Recent studies in terminal patients of hepatitis B and C have shown MSCs transplantation can improve hepatic function, including cirrhotic patients.

Objetivos - Metodologia - Resultados - Discussão dos Resultados/Objectives - Methodology - Results - Discussion of Results/Objetivos - Metodología - Resultados - Discusión de los resultados

Objectives: To evaluate whether hepatitis C drugs sofosbuvir and daclatasvir treatment affects MSCs normal functions.

Methodology: Human chorion-derived MSCs were analyzed for autophagy, cell viability and migration capacity assays. Cells were treated for 24h and 72h with 230ng/mL and 620ng/mL sofosbuvir and 400ng/mL and 1000ng/mL daclatasvir, respectively, in addition to a group with the highest concentrations of both drugs combined. These drugs concentrations were defined using hepatitis C patient’s serum concentrations reported in the literature. Viability and autophagy were assessed by markers annexin V-FITC, propidium iodide and acridin orange, and analyzed by flow citometry. Random migration capacity was assessed by wound healing assay and the distance between cells in the wound was measured in 5 different sites per image using Image J software.

Results and Discussion: We found no difference between treatments and control group for neither of the parameters proposed. These preliminary results indicate sofosbuvir and daclatasvir hepatitis C drug treatment does not impair cell viability nor does it alter the autophagy or the migratory capacity of MSCs, thus preserving these MSCs normal functions. These results indicate cell therapy with MSCs could be performed concomitantly with treatment with these drugs.

Considerações Finais/Final considerations/Consideraciones finales

More experiments are necessary to determine whether MSCs immunomodulatory capacity also remain impaired by hepatitis C drug treatment, thus making these cells candidates for concomitant cell therapy for reducing liver inflammation in this disease.

Palavras-chave/Key words/Palabras clave

MSCs, human mesenchymal stem cells, sofosbuvir, daclatasvir, in vitro, cell therapy, hepatitis

Área

Mesenchymal stem cells/adultas

Autores

MICHELE ARAMBURU SERAFINI, Raquel Ayres, Ana Carolina Henzel Raymundo, Dienifer Hermann Sirena Sirena, Diórlon Nunes Machado, Eduardo Cremonese Filippi-Chiela, Anelise Bergmann Araújo, Themis Reverbel da Silveira, Mário Reis Álvares-da-Silva, Fabiany da Costa Gonçalves, Ana Helena da Rosa Paz