脂肪间充质干细胞治疗急性肝损伤的分子机制

Molecular mechanism of adipose tissue-derived mesenchymal stem cells in treatment of acute liver injury

背景:急性肝损伤是由多种病因诱发的肝脏损害,如未及时治疗则会发展成急性肝衰竭,严重影响患者的生命安全。由于肝脏是人体最大的免疫器官和代谢器官,目前治疗急性肝损伤尚无最优方案。脂肪间充质干细胞因具有多向分化潜能和免疫调节活性已逐渐成为治疗急性肝损伤的有效工具。目的:综述目前脂肪间充质干细胞及其经不同方式修饰后治疗急性肝损伤的进展和分子机制。方法:从PubMed、Web of Science与中国知网数据库中检索2000-2023年发表的相关文献,以“Acute liver injury,liver injury,Adipose tissue-derived mesenchymal stem cell,liver Injury Repair,stem cell transplantation,stem cell repair,Cell surface engineering,stem cell modification”为英文检索词,以“急性肝损伤,肝损伤,脂肪间充质干细胞,肝损伤修复,干细胞移植,干细胞修复,干细胞修饰”为中文检索词,最终检索筛选出该领域最新研究进展的62篇文献进行归纳分析。结果与结论:(1)脂肪间充质干细胞作为一种具有多向分化潜能的干细胞治疗急性肝损伤具有生物学优势,较其他两种主要间充质干细胞类型——骨髓间充质干细胞和脐带间充质干细胞具有来源丰富、获取便捷、医学伦理问题少的特点,且较骨髓间充质干细胞的自我更新能力强。(2)脂肪间充质干细胞可以通过降低免疫反应、分化为肝细胞、分泌生长因子和外泌体等多种途径,降低血清炎症因子表达,减少肝脏组织炎性细胞浸润,抑制细胞焦亡和自噬,发挥抗凋亡作用,促进肝窦内皮细胞和肝细胞再生等分子机制改善肝损伤;目前尚无研究表明何种机制为脂肪间充质干细胞治疗急性肝损伤的最佳机制,多数观点认为这些分子机制之间相互影响相互作用协同发挥治疗作用。(3)生物材料修饰和药物预处理等方式可以提升脂肪间充质干细胞治疗急性肝损伤的疗效:一方面,生物材料和药物修饰可以提升脂肪间充质干细胞自身的功能,如提高增殖迁移能力,上调其分泌的生长因子水平,增强抗炎能力等,从而促进脂肪间充质干细胞在损伤部位存活;另一方面,生物材料和药物修饰可以抑制损伤部位炎性细胞活化,促进血管生长,改善损伤部位环境从而提高移植成功率。(4)总之,脂肪间充质干细胞可以通过分泌生长因子和外泌体、发挥免疫调节作用及促进肝脏再生等途径在治疗急性肝损伤中发挥重要作用。随着科学技术的发展,生物材料与药物修饰可以提升脂肪间充质干细胞的自我更新能力,改善急性肝损伤的局部微环境,为进一步促进脂肪间充质干细胞治疗急性肝损伤的临床应用提供新的思路。

BACKGROUND:Acute liver injury can result from a variety of causes,and if not treated in time,it will develop into acute liver failure and seriously affect the life safety of patients.As the liver is the largest immune organ and metabolic organ,there is no optimal treatment for acute liver injury.The adipose tissuederived mesenchymal stem cell has multi-differentiation potential and immunomodulatory activity,so it has been gradually becoming an effective tool for the treatment of acute liver injury.OBJECTIVE:To review the progress and molecular mechanism of adipose tissue-derived mesenchymal stem cell and its modification in different ways in the treatment of acute liver injury.METHODS:Relevant articles published from 2000 to 2023 were retrieved from PubMed,Web of Science,and CNKI databases.English search terms were“acute liver injury,liver injury,adipose tissue-derived mesenchymal stem cell,liver injury repair,stem cell transplantation,stem cell repair,cell surface engineering,stem cell modification.”Chinese search terms were“acute liver injury,liver injury,adipose tissue-derived mesenchymal stem cell,liver injury repair,stem cell transplantation,stem cell repair,stem cell modification.”Totally 62 articles of the latest research progress in this field were summarized and analyzed.RESULTS AND CONCLUSION:(1)Adipose tissue-derived mesenchymal stem cell as a potential stem cell with multi-directional differentiation has biological advantages in the treatment of acute liver injury.Compared with the other two major types of mesenchymal stem cell that is bone marrow mesenchymal stem cell and umbilical cord mesenchymal stem cell,they are more widely sourced,easily accessible and have fewer ethical issues,and more self-renewal than bone marrow mesenchymal stem cell.(2)Adipose tissue-derived mesenchymal stem cell may play a therapeutic role in acute liver injury by regulating immune responses,differentiating into hepatocytes,and secreting growth factors and exosomes.It can reduce the expression of inflammatory factors in serum and the infiltration of inflammatory cells in liver tissue,also can inhibit the pyroptosis and autophagy levels to promote regeneration of sinusoidal endothelial cells and hepatocyte,and ultimately improve liver damage.At present,no studies have shown which mechanism is the best mechanism for adipose tissuederived mesenchymal stem cells to treat acute liver injury,and most opinions believe that these molecular mechanisms interact with each other to play a synergistic role in treatment.(3)Biomaterials modification and drug pretreatment can improve the efficacy of adipose tissue-derived mesenchymal stem cell in the treatment of acute liver injury.On the one hand,biomaterials and drug modifications can enhance the functions of adipose tissue-derived mesenchymal stem cell,such as enhancing the ability of proliferation and migration,increasing the level of growth factors secreted,and enhancing the anti-inflammatory ability and promoting the survival of adipose mesenchymal stem cells at the injury site.On the other hand,biomaterials and drug modifications can inhibit the activation of inflammatory cells at the injured site and promote the growth of blood to improve the success rate of transplantation.(4)In summary,adipose tissue-derived mesenchymal stem cell plays an important role in the treatment of acute liver injury by secreting growth factors and exosomes,regulating the immune response,and promoting liver regeneration.With the development of science and technology,biomaterials and drug modification can enhance the self-renewal ability of adipose tissue-derived mesenchymal stem cell and improve the local microenvironment of acute liver injury.It provides a new way to promote the clinical application of adipose tissue-derived mesenchymal stem cell in the treatment of acute liver injury.