Autologous bone marrow-derived mesenchymal stem cell transplantation promotes liver regeneration after portal vein embolization in cirrhotic rats

• Published in: The Journal of surgical research Vol. 184; no. 2; pp. 1161 - 1173
• Main Authors: Li, Tingjun, MD, PhD, Zhu, Jin, MD, PhD, Ma, Kuansheng, MD, PhD, Liu, Nianzhou, MD, Feng, Kai, MD, Li, Xiaowu, MD, Wang, Shuguang, MD, PhD, Bie, Ping, MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2013
• Subjects: Animals; Biomarkers - metabolism; Bone Marrow Cells - cytology; Bone mesenchymal stem cells (BMSCs); Cell Differentiation - physiology; Disease Models, Animal; Embolization, Therapeutic - methods; Hepatocyte Growth Factor - metabolism; Hepatocytes - cytology; Hepatocytes - metabolism; Hepatocytes differentiation; Interleukin-10 - metabolism; Liver Cirrhosis - metabolism; Liver Cirrhosis - physiopathology; Liver Cirrhosis - therapy; Liver regeneration; Liver Regeneration - physiology; Male; Matrix Metalloproteinase 9 - metabolism; Mesenchymal Stem Cell Transplantation - methods; Portal Vein - physiology; Portal vein embolization (PVE); Rats; Rats, Sprague-Dawley; Stem cell transplantation; Surgery; Transplantation, Autologous; Vascular Endothelial Growth Factor A - metabolism; Stem cell transplantation; Portal vein embolization (PVE); Hepatocytes differentiation; Liver regeneration; Bone mesenchymal stem cells (BMSCs)
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2013.04.054

Abstract Background Preexisting cirrhosis usually leads to an inadequate and delayed regeneration of the future liver remnant (FLR) after portal vein embolization (PVE). Bone marrow-derived mesenchymal stem cells (BMSC) are promising candidates for therapeutic applications in liver diseases. In this study, the efficacy of autologous BMSCs transplantation to promote FLR regeneration was investigated in a rat cirrhotic model. Methods Autologous BMSCs were expanded and labeled with PKH26, and then were injected immediately into nonembolized lobes after PVE through portal vein in cirrhotic rat. At 7, 14, and 28 d after this, liver weight and Ki-67 labeling index were measured, and blood analysis was performed. Cirrhotic degree of FLR was assessed by hydroxyproline content assay and histopathology. Gene expressions of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), interleukin-10 (IL-10), and matrix metalloproteinase-9 (MMP-9) were detected with real-time reverse transcriptase-polymerase chain reaction. Distribution and hepatocyte differentiation of BMSCs in FLR were determined by confocal microscopy. Results Autologous BMSCs significantly increased the FLR weight ratio to the total liver and the Ki-67 labeling index, and serum albumin levels were significantly higher and total bilirubin levels were significantly lower in the BMSCs group compared with the controls without BMSCs transplantation 14 and 28 d post-PVE. BMSCs significantly decreased the hydroxyproline content and collagen accumulation, up-regulated the expressions of HGF, IL-10, VEGF, and MMP-9 28 d post-PVE, and expressed hepatocyte-specific markers, such as α-fetoprotein, cytokeratin 18, and albumin in a time-dependent manner in FLR. Conclusions Autologous BMSCs can differentiate into hepatocyte and promote FLR regeneration after PVE in cirrhotic liver, which may be through improving local microenvironment by decreasing cirrhosis, up-regulating the gene expressions of VEGF, HGF, IL-10, and MMP-9.