Adas Gokhan, Koc Bora, Adas Mine, Duruksu Gokhan, Subasi Cansu, Kemik Ozgur, Kemik Ahu, Sakiz Damlanur, Kalayci Mustafa, Purisa Sevim, Unal Seda, Karaoz Erdal
Department of Surgery, Bakirkoy Dr.Sadi Konuk Training and Research Hospital, Istanbul, Turkey.
Faculty of Medicine, Istanbul Training Hospital, Department of Surgery, Baskent University, Oymaci Sok. No:7, 34662, Altunizade Uskudar, Istanbul, Turkey.
Langenbecks Arch Surg. 2016 Aug;401(5):725-40. doi: 10.1007/s00423-016-1380-9. Epub 2016 Apr 19.
The study aims to determine the effects of mesenchymal stem cell (MSC) therapy and a combination therapy of MSCs transfected with vascular endothelial growth factor (VEGF) for liver regeneration after major resection.
Thirty-eight rats were divided into four groups: group 1: control (sham operation); group 2: control (70 % hepatic resection); group 3: 70 % hepatic resection + systemically transplanted MSCs; and group 4: 70 % hepatic resection + systemically transplanted MSCs transfected with the VEGF gene. MSCs were injected via the portal vein route in study groups 3 and 4. Expression levels of VEGF, fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor (TGF), hepatocyte growth factor (HGF), and augmenter of liver regeneration (ALR) were analyzed in the remnant liver tissue. We investigated the levels of angiogenic factors, VEGF-receptor, angiopoietin-1 (Angpt1) and Angpt2. Biochemical parameters of liver function in blood samples were measured and a histologic assessment of the livers was performed. The postoperative liver weight and volume of each rat were measured 14 days after surgery.
The expression levels of all measured growth factors were significantly increased in groups 3 and 4 compared to the control groups. The levels of Angpt1 and Angpt2 correlated with levels of VEGF and thus were also significantly higher in the study groups. There were significant differences between the estimated liver weights and volumes of group 4 and the resected controls in group 2. With the exception of portal inflammation, levels of all histological parameters were observed to be higher in MSC-treated groups when compared with the resected controls in group 2.
Transplanted stem cells and MSCs transfected with VEGF significantly accelerated many parameters of the healing process following major hepatic resection. After the injection of MSCs and VEGF-transfected MSCs into the portal vein following liver resection, they were engrafted in the liver. They increased bile duct and liver hepatocyte proliferation, and secreted many growth factors including HGF, TGFβ, VEGF, PDGF, EGF, and FGF via paracrine effects. These effects support liver function, regeneration, and liver volume/weight.
本研究旨在确定间充质干细胞（MSC）治疗以及用血管内皮生长因子（VEGF）转染的MSC联合治疗对大鼠肝大部切除术后肝再生的影响。
38只大鼠分为四组：第1组：对照组（假手术）；第2组：对照组（70%肝切除）；第3组：70%肝切除+全身移植MSC；第4组：70%肝切除+全身移植VEGF基因转染的MSC。第3组和第4组经门静脉途径注射MSC。分析残余肝组织中VEGF、成纤维细胞生长因子（FGF）、血小板衍生生长因子（PDGF）、表皮生长因子（EGF）、转化生长因子（TGF）、肝细胞生长因子（HGF）和肝再生增强因子（ALR）的表达水平。我们研究了血管生成因子、VEGF受体、血管生成素-1（Angpt1）和血管生成素-2（Angpt2）的水平。检测血样中肝功能的生化参数，并对肝脏进行组织学评估。术后14天测量每只大鼠的肝脏重量和体积。
与对照组相比，第3组和第4组中所有检测的生长因子表达水平均显著升高。Angpt1和Angpt2的水平与VEGF水平相关，因此在研究组中也显著更高。第4组的估计肝脏重量和体积与第2组的切除对照组之间存在显著差异。与第2组的切除对照组相比，除门静脉炎症外，MSC治疗组的所有组织学参数水平均较高。
移植的干细胞和VEGF转染的MSC显著加速了肝大部切除术后愈合过程的许多参数。肝切除术后将MSC和VEGF转染的MSC注入门静脉后，它们在肝脏中植入。它们增加了胆管和肝细胞增殖，并通过旁分泌作用分泌了许多生长因子，包括HGF、TGFβ、VEGF、PDGF、EGF和FGF。这些作用支持肝功能、肝再生以及肝脏体积/重量。
