Kim Yan S, Lupatov Alexey Yu, Burunova Veronika V, Bagmet Nikolay N, Chardarov Nikita K, Malov Svyatoslav L, Kholodenko Roman V, Shatverian Garnik A, Manukyan Garik V, Yarygin Konstantin N, Kholodenko Irina V
Laboratory of Cell Biology, V.N. Orekhovich Institute of Biomedical Chemistry, 119121 Moscow, Russia.
Department of Abdominal Surgery and Oncology, Laboratory of Emergency Surgery and Portal Hypertension, Petrovsky National Research Centre of Surgery, 119435 Moscow, Russia.
Int J Mol Sci. 2024 Dec 13;25(24):13374. doi: 10.3390/ijms252413374.
Every 25th death worldwide is associated with liver pathology. The development of novel approaches to liver diseases therapy and protocols for maintaining the vital functions of patients on the liver transplant waiting list are urgently needed. Resident mesenchymal stem cells (MSCs) play a significant role in supporting liver tissue integrity and improve the liver condition after infusion. However, it remains unclear whether MSCs isolated from chronically inflamed livers are similar in their basic cellular properties to MSCs obtained from healthy livers. We applied a large array of tests to compare resident MSCs isolated from apparently normal liver tissue and from chronically inflamed livers of patients with fibrosis, cirrhosis, and viral hepatitis. Chronic inflammatory environment did not alter the major cellular characteristics of MSCs, including the expression of MSC markers, stem cell markers, adhesion molecules, and the hallmarks of senescence, as well as cell proliferation, migration, and secretome. Only the expression of some immune checkpoints and toll-like receptors was different. Evidently, MSCs with unchanged cellular properties are present in human liver even at late stages of inflammatory diseases. These cells can be isolated and used as starting material in the development of cell therapies of liver diseases.
全球每25例死亡中就有1例与肝脏病变相关。迫切需要开发治疗肝脏疾病的新方法以及制定维持肝移植等待名单上患者生命功能的方案。肝内间充质干细胞(MSCs)在维持肝组织完整性及输注后改善肝脏状况方面发挥着重要作用。然而,从慢性炎症肝脏中分离出的间充质干细胞在其基本细胞特性上是否与从健康肝脏中获得的间充质干细胞相似仍不清楚。我们应用了大量测试来比较从明显正常肝组织以及患有纤维化、肝硬化和病毒性肝炎的患者慢性炎症肝脏中分离出的肝内间充质干细胞。慢性炎症环境并未改变间充质干细胞的主要细胞特征,包括间充质干细胞标志物、干细胞标志物、黏附分子的表达以及衰老的特征,还有细胞增殖、迁移和分泌组。只有一些免疫检查点和Toll样受体的表达有所不同。显然,即使在炎症疾病的晚期,人类肝脏中仍存在细胞特性未改变的间充质干细胞。这些细胞可以被分离出来,并用作肝脏疾病细胞治疗开发的起始材料。