Advantages of adipose tissue stem cells over CD34+ mobilization to decrease hepatic fibrosis in Wistar rats

De Luna Saldivar, Marcela M. y Marino Martínez, Iván Alberto y Franco Molina, Moisés Armides y Rivera Morales, Lydia Guadalupe y Alarcón Galván, Gabriela y Cordero Pérez, Paula y Rojas Martínez, Augusto y Rodríguez Padilla, Cristina y Muñoz Espinosa, Linda Elsa (2019) Advantages of adipose tissue stem cells over CD34+ mobilization to decrease hepatic fibrosis in Wistar rats. Annals of hepatology, 18 (4). pp. 620-626. ISSN 1665-2681

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Resumen

Introduction and Objectives: Chronic liver inflammation may lead to hepatic cirrhosis, limiting its regenerative capacity. The clinical standard of care is transplantation, although stem cell therapy may be an alternative option. The study aim was to induce endogenous hematopoietic stem cells (HSCs) with granulocyte colony stimulating factor (G-CSF) and/or intravenous administration of adipose tissue-derived mesenchymal stem cells (MSCs) to decrease hepatic fibrosis in an experimental model. Material and methods: A liver fibrosis model was developed with femaleWistar rats via multiple intraperitoneal doses of carbon tetrachloride. Three rats were selected to confirm cirrhosis, and the rest were set into experimental groups to evaluate single and combined therapies of G-CSF-stimulated HSC mobilization and intravenous MSC administration. Results: Treatment with MSCs and G-CSF significantly improved alanine amino transferase levels, while treatment with G-CSF, MSCs, and G-CSF + MSCs decreased aspartate amino transferase levels. Hepatocyte growth factor (HGF) and interleukin 10 levels increased with MSC treatment. Transforming growth factor levels were lower with MSC treatment. Interleukin 1 and tumor necrosis factor alpha levels decreased in all treated groups. Histopathology showed that MSCs and G-CSF reduced liver fibrosis from F4 to F2. Conclusions: MSC treatment improves liver function, decreases hepatic fibrosis, and plays an antiinflammatory role;it promotes HGF levels and increased proliferating cell nuclear antigen when followed by MSC treatment mobilization using G-CSF. When these therapies were combined, however, fibrosis improvement was less evident.

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