Maorong Wang1, Xin Zhang2, X I Xiong2, Zhiguo Yang2, Ping Li2, Jie Wang2, Y U Sun3, Zhijian Yang4, Robert M Hoffman5. 1. Liver Disease Center of PLA, Department of Infectious Disease, Nanjing University of Chinese Medicine Affiliated Bayi Hospital, Nanjing, P.R. China maorongwang@126.com all@anticancer.com. 2. Liver Disease Center of PLA, Department of Infectious Disease, Nanjing University of Chinese Medicine Affiliated Bayi Hospital, Nanjing, P.R. China. 3. Origin Biosciences Inc., Nanjing, P.R. China. 4. Origin Biosciences Inc., Nanjing, P.R. China AntiCancer Inc., San Diego, CA, U.S.A. 5. AntiCancer Inc., San Diego, CA, U.S.A. Department of Surgery, University of California San Diego, San Diego, CA, U.S.A. maorongwang@126.com all@anticancer.com.
Abstract
BACKGROUND/AIM: The aim of this study was to investigate the effect of bone-marrow mesenchymal stem cells (BMSCs) on repair of liver damage in a carbon tetrachloride (CCl4)-induced mouse model of chronic liver damage. MATERIALS AND METHODS: Green fluorescent protein (GFP)-expressing BMSCs, isolated from GFP transgenic mice, were transplanted into mice with chronic liver damage induced by CCl4 The GFP-expressing BMSCs in livers were detected by fluorescence microscopy. Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured for assessment of liver function. Liver histopathology was performed to assess liver damage. mRNA and protein expression of liver-associated markers albumin (Alb) and alpha-fetoprotein (Afp) were detected to confirm the hepatic differentiation of BMSCs in the liver. Immunostaining for the expression of interleukin-10 (IL-10) and matrix metallopeptidase-9 (MMP-99), and enzyme-linked immunosorbent assay for the secretion of type III collagen and lamininin was carried out. RESULTS: After BMSC transplantation, GFP-expressing BMSCs were detected in the peri-portal and injured areas of the CCL4-injured liver. mRNA and protein expressions of Alb and Afp were significantly increased in BMSC-transplanted liver. Mice treated with BMSCs displayed reduced serum levels of ALT and AST, and CCl4-induced histopathological changes in livers were repaired. BMSC transplantation increased the production of IL-10 and inhibited the expression of MMP-9, as well as the secretion of type III collagen and lamininin. CONCLUSION: BMSCs transplanted into mice can migrate into damaged liver, differentiate into hepatocytes and promote recovery from chemically-induced liver damage. Promotion of IL-10 and inhibition of MMP-9 by transplanted BMSCs may be involved in the anti-inflammatory and anti-fibrotic action of BMSCs.
BACKGROUND/AIM: The aim of this study was to investigate the effect of bone-marrow mesenchymal stem cells (BMSCs) on repair of liver damage in a carbon tetrachloride (CCl4)-induced mouse model of chronic liver damage. MATERIALS AND METHODS: Green fluorescent protein (GFP)-expressing BMSCs, isolated from GFP transgenic mice, were transplanted into mice with chronic liver damage induced by CCl4 The GFP-expressing BMSCs in livers were detected by fluorescence microscopy. Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured for assessment of liver function. Liver histopathology was performed to assess liver damage. mRNA and protein expression of liver-associated markers albumin (Alb) and alpha-fetoprotein (Afp) were detected to confirm the hepatic differentiation of BMSCs in the liver. Immunostaining for the expression of interleukin-10 (IL-10) and matrix metallopeptidase-9 (MMP-99), and enzyme-linked immunosorbent assay for the secretion of type III collagen and lamininin was carried out. RESULTS: After BMSC transplantation, GFP-expressing BMSCs were detected in the peri-portal and injured areas of the CCL4-injured liver. mRNA and protein expressions of Alb and Afp were significantly increased in BMSC-transplanted liver. Mice treated with BMSCs displayed reduced serum levels of ALT and AST, and CCl4-induced histopathological changes in livers were repaired. BMSC transplantation increased the production of IL-10 and inhibited the expression of MMP-9, as well as the secretion of type III collagen and lamininin. CONCLUSION: BMSCs transplanted into mice can migrate into damaged liver, differentiate into hepatocytes and promote recovery from chemically-induced liver damage. Promotion of IL-10 and inhibition of MMP-9 by transplanted BMSCs may be involved in the anti-inflammatory and anti-fibrotic action of BMSCs.
Authors: Dina M Rostom; Noha Attia; Hoda M Khalifa; Maha W Abou Nazel; Eshrak A El Sabaawy Journal: Tissue Eng Regen Med Date: 2020-06-06 Impact factor: 4.169
Authors: Yasmine H Khalifa; Ghada M Mourad; Wahid M Stephanos; Sahar A Omar; Radwa A Mehanna Journal: Biomed Res Int Date: 2019-11-06 Impact factor: 3.411