Objetive To summarize the mechanism and the application of the research on liver regeneration. Methods The related literatures about enteral liver regeneration in recent years were reviewed. Results Even though liver regeneration after liver resection has been widely studied, we can get better understanding from new clinical application. The process of regeneration induced liver injury rarely occurs in the normal liver. Many studies have focused on the mechanism of liver cell regeneration after liver injury. For example, the study of liver regeneration related factors and liver regenerative cells, but the specific mechanism is still not very clear. Recent techniques using the obvious progress in understanding liver regeneration are portal vein embolization and the associating liver partition and portal vein ligation for staged hepatectomy. Living donor liver transplantation is one of the most significant clinical outcomes of research on liver regeneration. Another involved in liver regeneration is the main field of stem cell therapy. Conclusion Great understanding liver regeneration should provide to the development of new treatment strategies and diagnostic procedures for various liver diseases.
ObjectiveTo investigate the role of endoplasmic reticulum stress in liver regeneration after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS).MethodsSeventy-two C57bl/6 mice were randomly divided into ALPPS group, portal vein ligation group (PVL group), and sham operation group (Sham group), 24 mice in each group. And then one-stage ALPPS operation, simple PVL, and sham operation will be performed. Six mice were randomized selected of the three groups on the 1st, 2nd, 4th, and 7th day after surgery, respectively, the liver weight to body weight ratio (FLR/BW) of each group was measured, and the liver tissues were taken for immunohistochemical staining to calculate the proportion of Ki-67 positive cells, Western blot was used to detect the expression levels of X-box binding protein 1 (XBP1) and inositol-requiring enzyme 1α (IRE1α) proteins.Results① FLR/BW: On the 4th day and the 7th day after operation, the FLR/BW of the Sham group, PVL group, and ALPPS group increased in sequence at the same time, and the difference between the three groups was statistically significant (P<0.05). ② Ki-67 positive cell ratio: On the 2nd day after operation, the ratio of Ki-67 positive cells in the Sham group, PVL group, and ALPPS group increased sequentially, and the difference between the two groups was statistically significant (P<0.05). On the 4th day after operation, the ratio of Ki-67 positive cells in the PVL group and the ALPPS group were still higher than that of the Sham group (P<0.05). ③ Expression levels of XBP1 and IRE1α: On the 2nd and 4th postoperative day, the expression levels of XBP1 and IRE1α in the ALPPS group were higher than those in the Sham group and the PVL group (P<0.05). On the 7th day after surgery, the expression levels of XBP1 and IRE1α in the ALPPS group were higher than those in the Sham group (P<0.05), while compared with the PVL group, the expression level of XBP1 in the ALPPS group was still higher (P<0.05).ConclusionsALPPS-induced liver regeneration is more advantageous than traditional PVL in mice. It may be attributed to the obvious endoplasmic reticulum stress activation after ALPPS leading to the up-regulation of IRE1α-XBP1 expression, which is involved in the regulation of hepatocyte cell cycle and promotes hepatocyte proliferation, thus promoting rapid liver regeneration.
ObjectiveTo summarize the current research status of the relationship between DNA methylation and liver regeneration.MethodThe related literatures at home and abroad were searched to review the studies on relationships between the methylation level of liver cells, regulation of gene expression, and methylation related proteins and liver regeneration.ResultsThe DNA methylation was an important epigenetic regulation method in vivo and its role in the liver regeneration had been paid more and more attentions in recent years. The existing studies had found the epigenetic phenomena during the liver regeneration such as the genomic hypomethylation, methylation changes of related proliferating genes and DNA methyltransferase and UHRF1 regulation of the liver regeneration.ConclusionsThere are many relationships between DNA methylation and liver regeneration. Regulation of liver regeneration from DNA methylation level is expected to become a reality in the near future.
Augmenter of liver regeneration (ALR) is a newly discovered cytokine that can promote liver regeneration and proliferation of damaged liver cells. In the renal tissue, ALR is mainly expressed in the cytoplasm of the medullary loops, collecting ducts and distal convoluted tubules in the renal medulla, and is low in the glomerular and cortical tubules. Various stimulation, such as ischemiacal, hypoxia, poisoning and inflammatory stimulation, can induce the expression of ALR in the epithelial cells of proximal tubule regeneration and the damaged areas of cortex, and participate in the repair process. Current studies have found that in acute kidney injury (AKI), exogenous ALR can protect renal tubular epithelial cells by inhibiting apoptosis of renal tubular epithelial cells, promoting proliferation of renal tubular epithelial cells, inhibiting the activities of inflammatory cells, and promoting the reduction of renal injury. This paper intends to review the basic characteristics of ALR and the pathogenesis of AKI, summarize the characteristics of the mechanism of ALR in AKI by combing the relevant literature on ALR and AKI in recent years, and provide knowledge reserve and direction reference for the in-depth study of ALR in kidney in the future.
ObjectiveTo investigate the expression of Lgr5 protein in regeneration tissue of remnant liver after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and its significance.MethodsA total of 120 male SD rats (200–240 g) were randomly equally divided into sham operation (SO) group, portal vein ligation (PVL) group, and ALPPS group using random number table method. The liver regeneration rate (LRR), liver function (AST and ALT), and the expressions of Ki-67 and Lgr5 in the right middle lobe of the liver were observed at day 1, 2, 4, and 7 after surgery.ResultsCompared with SO group, the LRRs and the Ki-67 protein expression positive rates and Lgr5 related protein expression levels in the right middle lobe of liver tissue were increased in the PVL group and ALPPS group at day 1, 2, and 4 after surgery (P<0.05), and the LRR was still increased at day 7 after surgery (P<0.05). The LRRs at day 4 and 7 after surgery in the ALPPS group were higher than those in the PVL group (P<0.05), the Ki-67 protein expression positive rates and Lgr5 related protein expression levels at day 2 and 4 after surgery in the ALPPS group were higher than those in the PVL group (P<0.05). The AST and ALT levels at day 1 and 2 after surgery in the ALPPS group and PVL group were higher than those in the SO group (P<0.05), which at day 1 after surgery in the ALPPS group were higher than those in the PVL group (P<0.05), but which returned to normal on day 4 after surgery.ConclusionsALPPS could promote liver regeneration better. Lgr5 is closely related to liver regeneration after ALPPS. Liver stem cells might be involved in liver regeneration after ALPPS.
Objective To summarize the research progress on the regulation of hepatic sinusoidal microenvironment to promote liver regeneration based on liver sinusoidal endothelial cells (LSECs), aiming to further clarify the mechanism of liver regeneration and provide new ideas and methods for clinical promotion of liver regeneration and prevention of liver failure. Method The basic and clinical research studies on LSECs and liver regeneration at home and abroad in recent years were searched and reviewed. Results Differentiated LSECs played an important role in liver regeneration, regulated the homeostasis of hepatic sinusoid microenvironment by paracrine and autocrine, and participated in the whole process of promoting liver regeneration, such as hepatocyte proliferation and neovascularization after acute and chronic liver injury. Conclusion In the process of liver regeneration after all kinds of acute and chronic liver injury, LSECs promote liver regeneration by regulating hepatic sinusoid microenvironment, which will provide new strategies and methods for clinical promotion of liver regeneration and prevention of liver failure after hepatectomy.
ObjectiveTo summarize the progress of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and evolution of surgical procedure improvement, so as to summarize experience in selecting appropriate surgical method for patients. MethodThe domestic and foreign literature on the evolution of ALPPS surgical procedure improvement in recent years was reviewed. ResultsIn the decade since the emergence of ALPPS, the ALPPS had been rapidly developed in the hepatobiliary surgery. The ALPPS promoted a rapid increase in future liver remnant during a relatively shorter period to contribute to resectability of liver tumors and reduce the rate of postoperative liver failure, the patients with intermediate to advanced and huge liver cancer could obtain the surgical radical resection. In recent years, the domestic and foreign experts had refined the ALPPS procedure, which mainly focused on the operation of hepatic section separation and hepatic artery flow restriction in stage Ⅰ surgery, including partial ALPPS, radiofrequency ablation ALPPS, tourniquet ALPPS, transcatheter arterial embolization ALPPS, hepatic artery ringed and operation ALPPS, as well as laparoscopic ALPPS and robotic ALPPS with minimally invasive approach. ConclusionsDespite the ongoing controversy over ALPPS, with the continuous progress and innovation of improved procedures and the utilization of laparoscope and robot in surgery, the trauma of ALPPS surgery has a further reduction, and the morbidity and mortality have gradually been decreased. It is believed that with the continuous advancement and improvement of ALPPS surgery technology, the indications and safety of ALPPS will be further enhanced, bringing hope to more patients with intermediate to advanced liver cancer with huge tumors.
ObjectiveTo understand the latest development in lineage tracing techniques and their applications in the study of liver regeneration mechanisms. MethodA review of domestic and international literature on the application of lineage tracing techniques in liver regeneration was conducted. ResultsA variety of more reliable and advanced lineage tracing techniques had been developed, such as single-cell RNA sequencing, DNA barcode technology, etc., providing powerful tools for a deeper understanding of the mechanisms of liver regeneration. The marked progress had been made in identifying the origins of liver regeneration cells, identifying liver regeneration areas, and studying the mechanisms of liver regeneration after injury. The lineage tracing techniques help to understand the position and function of different types of liver cells within the liver structure, revealing the regenerative potential and contribution of different subpopulations of liver cells. Moreover, these techniques had supported the phenomenon of transdifferentiation between the hepatocytes and the bile duct cells under chronic liver injury conditions, aiding in understanding the specific roles of key signaling pathways in liver regeneration, such as Wnt/β-catenin, Hippo/YAP, and Notch signaling pathways.ConclusionsAlthough lineage tracing techniques have made marked progress in liver regeneration research, liver regeneration is a complex and important physiological process, and the technique still has limitations, such as challenges in marker specificity, longer research cycles and higher costs, potential limitations in translating from animal models to human clinical applications, inability to solve all questions about liver regeneration mechanisms, and ethical and legal issues. Therefore, more in-depth and comprehensive research is still needed to reveal more details of liver regeneration mechanism.
ObjectiveTo explore the safety and efficacy of preoperative liver regeneration and then two-stage liver resection for advanced hepatic alveolar echinococcosis (HAE) patients pre-evaluating insufficient future liver remnant (FLR) after resection. MethodThe clinical data of the advanced HAE patients who were expected to have insufficient FLR after liver resection and underwent two-step liver resection in the Sichuan Provincial People’s Hospital from December 2016 to December 2022 were retrospectively collected and summarized. ResultsA total of 11 patients with advanced HAE pathologically confirmed were collected. Among them, 2 cases underwent portal vein embolization (PVE), 2 cases underwent liver vein deprivation (LVD), and 7 cases underwent associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) to promote residual liver regeneration in the first stage. The FLR/standard liver volume (SLV) exceeded the surgical requirement standard of 40%. Then the ex-vivo liver resection and autotransplantation, or directly radical liver resection was performed in the second stage. Only one patient underwent surgery to remove packed gauze on day 3 postoperatively due to massive intraoperative bleeding (approximately 4 000 mL). The median (P25, P75) follow-up time after surgery was 36 (15, 75) months, only one case was found to relapse at the third year after surgery and underwent surgical resection again, and the rest patients had no recurrence, long-term complications, or death. ConclusionsBased on the results from these cases, applying PVE, LVD, or ALPPS in the patients with advanced HAE who were expected to have insufficient FLR after resection aids to residual liver regeneration, creating conditions for the second stage radical resection. The second stage treatment including ex-vivo liver resection and autotransplantation or directly radical liver resection could achieve good results and is feasible and safe, which brings a hope of survival for the advanced HAE patients who could not previously undergo curative resection. However, this treatment strategy still incurs high costs and requires further optimization in the future.