肝星型细胞分离方法和功能研究进展

Update on isolation and functional research of hepatic stellate cells

摘要:

肝星型细胞 (Hepatic stellate cells, HSCs)，又叫储脂细胞 (Fat-storing cells, FSCs) 或脂肪细胞 (lipocytes)，是肝脏固有的非实质细胞类型之一，存在于狄氏腔内，以脂滴的形式储存人体维生素A总量的50%–80%。原代HSCs分离方法，目前主要集中于密度梯度离心法结合离心淘洗、HSCs高侧向角的流式分选法、紫外激发的自发荧光或特异性抗体标记的流式细胞术等，将为HSCs生理和病理研究提供坚实的基础。近年来，HSCs的研究蓬勃发展，合作领域不断拓宽。生理状态下，HSCs处于静息状态，合成细胞外基质 (Extracellular matrix, ECM) 并维持其稳态，同时广泛摄取和储存维生素A，并具有调节肝细胞再生的功能；而病理状态下，HSCs在肝损伤和持续性刺激条件下被激活，增殖活性明显增强，脂滴减少或消失，ECM合成也明显增加，具有收缩性，同时分泌多种促炎因子和粘附分子，并向肌成纤维细胞转变，表明HSCs的活化是肝纤维化发生发展过程中的关键环节之一。有关HSCs的分离和功能研究一直是肝脏细胞学和肝脏病理学研究的热点之一。文中我们将系统总结和探讨HSCs的分离方法和改进策略，及其功能研究进展和具有潜在价值的研究方向。

Abstract:

Hepatic stellate cells (HSCs), also called Ito cells or lipocytes, are one of inherent liver nonparenchymal cell types located in the Dissé space between hepatocytes and sinusoidal endothelial cells, and account for up to 50%–80% of vitamin A in the form of lipid drops. The methods of primary HSCs isolation mainly focus on density gradient centrifugation combined with centrifugal elutriation, side scatter-activated cell sorting, UV-excited autofluorescence or antibody-based flow cytometry, etc., and will provide solid foundation for the research on physiological and pathological HSCs function. The research of this vitamin A-storing cells has developed and expanded vigorously. In physiological conditions, HSCs are quiescent and play pivotal roles in the synthesis of extracellular matrix (ECM) to maintain its stability with broad uptake and storage of vitamin A, and also regulate liver regeneration. But in pathological conditions, HSCs are activated by constant stimulations or liver injury, then with activated proliferation, reduced lipid drops, and increased ECM synthesis. Morphology of these cells also changes from the star-shaped stellate cells to that of fibroblasts or myofibroblasts with obvious contractibility and secretion of cytokines and chemokines including a variety of proinflammatory factors and adhesion molecules, suggesting that the activation of HSCs is one of the key events in the development of liver fibrosis. Study on the isolation and function of HSCs is always one of the hot topics for liver biology. In this review, we systematically summarize and discuss the recent advances in our understanding of the isolation methods and improvements of HSCs, and functional research of HSCs biology in health and disease, as well as potential directions.