Marcela M De Luna-Saldivar1, Iván A Marino-Martinez2, Moisés A Franco-Molina3, Lydia G Rivera-Morales3, Gabriela Alarcón-Galván4, Paula Cordero-Pérez5, Augusto Rojas-Martínez6, Cristina Rodríguez-Padilla3, Linda E Muñoz-Espinosa7. 1. Department of Immunology and Virology, Biological Sciences Faculty, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, NL, Mexico; Liver Unit, Department of Internal Medicine, "Dr. José E. González" University Hospital, Universidad Autónoma de Nuevo León, Monterrey, NL, Mexico. 2. Center for Research and Development in Health Sciences, Universidad Autónoma de Nuevo León, Monterrey, NL, Mexico. 3. Department of Immunology and Virology, Biological Sciences Faculty, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, NL, Mexico. 4. Basic Science Department, School of Medicine, UDEM, Universidad de Monterrey, San Pedro Garza García, NL, Mexico. 5. Liver Unit, Department of Internal Medicine, "Dr. José E. González" University Hospital, Universidad Autónoma de Nuevo León, Monterrey, NL, Mexico. 6. Escuela de Medicina, Instituto Tecnológico y de Estudios Superiores de Monterrey, Monterrey, NL, Mexico. 7. Liver Unit, Department of Internal Medicine, "Dr. José E. González" University Hospital, Universidad Autónoma de Nuevo León, Monterrey, NL, Mexico. Electronic address: linda_uanl@hotmail.com.
Abstract
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 female Wistar 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 β levels were lower with MSC treatment. Interleukin 1β 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 anti-inflammatory 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.
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 female Wistar 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 β levels were lower with MSC treatment. Interleukin 1β 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 anti-inflammatory 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.
Authors: Fatemeh Dehghani Nazhvani; Iman Haghani; Seifollah Dehghani Nazhvani; Fatemeh Namazi; Abbas Ghaderi Journal: Ann Med Surg (Lond) Date: 2020-10-24