Macedo Francisco Igor, Eid Joseph J, Decker Milessa, Herschman Barry, Negussie Edsa, Mittal Vijay K
Department of Surgery, Providence Hospital and Medical Centers, Michigan State University College of Human Medicine, Southfield, Michigan.
Department of Surgery, Providence Hospital and Medical Centers, Michigan State University College of Human Medicine, Southfield, Michigan.
J Surg Res. 2018 Mar;223:215-223. doi: 10.1016/j.jss.2017.11.032. Epub 2017 Dec 22.
Liver regeneration involves hyperplasia and hypertrophy of hepatic cells. The capacity of macroscopic liver tissue to regenerate in ectopic sites is unknown. We aim to develop a novel in vivo model of ectopic liver survivability and regeneration and assess its functionality.
Adult male Sprague-Dawley rats (n = 23) were divided into four groups: (1) single-stage (SS) group, wedge liver resection was performed, and the parenchyma was directly implanted into the omentum; (2) double-stage (DS) group, omentum pedicle was transposed over the left hepatic lobe followed by wedge liver resection along with omental flap; (3) Biogel + DS group, rats received intraperitoneal injection of inert polymer particles prior to DS; (4) Biogel + DS + portal vein ligation (PVL) group, Biogel + DS rats underwent subsequent PVL. Hepatobiliary iminodiacetic acid scintigraphy assessed bile excretion from ectopic hepatic implants.
Histologically, the scores of necrosis (P < 0.001) and fibrosis (P = 0.004) were significantly improved in rats undergoing DS procedure (groups 2, 3, and 4) compared with the SS group. Biogel rats (Biogel + DS and Biogel + DS + PVL) demonstrated statistically increased scores of bile duct neoformation (P = 0.002) compared to those without the particles (SS and DS). Scintigraphy demonstrated similar uptake of radiotracer by ectopic hepatic implants in groups 2, 3, and 4.
Omental transposition provided adequate microcirculation for proliferation of ectopic hepatic cells after liver resection. Inert polymers enhanced the regeneration by promoting differentiation of new bile ducts. The ectopic hepatic implants showed preserved function on scintigraphy. This model provides insights into the capacity of liver parenchyma to regenerate in ectopic sites and the potential as therapeutic target for cell therapy in end-stage liver disease.
肝再生涉及肝细胞的增生和肥大。宏观肝组织在异位部位再生的能力尚不清楚。我们旨在建立一种新型的异位肝存活和再生的体内模型，并评估其功能。
将成年雄性Sprague-Dawley大鼠（n = 23）分为四组：（1）单阶段（SS）组，行楔形肝切除术，将肝实质直接植入大网膜；（2）双阶段（DS）组，将带蒂大网膜移位至左肝叶上方，随后行楔形肝切除术并连同网膜瓣；（3）生物凝胶+DS组，大鼠在DS术前接受腹腔注射惰性聚合物颗粒；（4）生物凝胶+DS+门静脉结扎（PVL）组，生物凝胶+DS大鼠随后接受PVL。肝胆亚氨基二乙酸闪烁扫描评估异位肝植入物的胆汁排泄。
组织学上，与SS组相比，接受DS手术的大鼠（第2、3和4组）的坏死评分（P < 0.001）和纤维化评分（P = 0.004）显著改善。与未使用颗粒的大鼠（SS和DS）相比，生物凝胶大鼠（生物凝胶+DS和生物凝胶+DS+PVL）的胆管新生评分在统计学上显著增加（P = 0.002）。闪烁扫描显示第2、3和4组异位肝植入物对放射性示踪剂的摄取相似。
网膜移位为肝切除术后异位肝细胞的增殖提供了充足的微循环。惰性聚合物通过促进新胆管的分化增强了再生。异位肝植入物在闪烁扫描中显示功能保留。该模型为肝实质在异位部位的再生能力以及作为终末期肝病细胞治疗的潜在靶点提供了见解。
