Xiang Wen, Wang Xinhe, Yu Xinghui, Xie Yan, Zhang Li, Lu Naiyan, Jiang Wentao
School of Medicine, Nankai University, Tianjin, China.
Department of Liver Transplantation, Tianjin First Central Hospital, Tianjin, China.
Stem Cells Int. 2023 Jan 9;2023:6890299. doi: 10.1155/2023/6890299. eCollection 2023.
Liver transplantation is limited by the insufficiency of liver organ donors when treating end-stage liver disease or acute liver failure (ALF). Ectodermal mesenchymal stem cells (EMSCs) derived from nasal mucosa have emerged as an alternative cell-based therapy. However, the role of EMSCs in acute liver failure remains unclear.
EMSCs were obtained from the nasal mucosa tissue of rats. First, EMSCs were seeded on the gelatin-chitosan scaffolds, and the biocompatibility was evaluated. Next, the protective effects of EMSCs were investigated in carbon tetrachloride- (CCl-) induced ALF rats. Finally, we applied an indirect coculture system to analyze the paracrine effects of EMSCs on damaged hepatocytes. A three-step nontransgenic technique was performed to transform EMSCs into hepatocyte-like cells (HLCs) in vitro.
EMSCs exhibited a similar phenotype to other mesenchymal stem cells along with self-renewal and multilineage differentiation capabilities. EMSC-seeded gelatin-chitosan scaffolds can increase survival rates and ameliorate liver function and pathology of ALF rat models. Moreover, transplanted EMSCs can secrete paracrine factors to promote hepatocyte regeneration, targeted migration, and transdifferentiate into HLCs in response to the liver's microenvironment, which will then repair or replace the damaged hepatocytes. Similar to mature hepatocytes, HLCs generated from EMSCs possess functions of expressing specific hepatic markers, storing glycogen, and producing urea.
These results confirmed the feasibility of EMSCs in acute hepatic failure treatment. To our knowledge, this is the first time that EMSCs are used in the therapy of liver diseases. EMSCs are expected to be a novel and promising cell source in liver tissue engineering.
在治疗终末期肝病或急性肝衰竭（ALF）时，肝移植受肝器官供体不足的限制。源自鼻黏膜的外胚层间充质干细胞（EMSCs）已成为一种替代性的细胞疗法。然而，EMSCs在急性肝衰竭中的作用仍不清楚。
从大鼠鼻黏膜组织中获取EMSCs。首先，将EMSCs接种在明胶-壳聚糖支架上，并评估其生物相容性。接下来，在四氯化碳（CCl）诱导的ALF大鼠中研究EMSCs的保护作用。最后，应用间接共培养系统分析EMSCs对受损肝细胞的旁分泌作用。采用三步非转基因技术在体外将EMSCs转化为肝细胞样细胞（HLCs）。
EMSCs表现出与其他间充质干细胞相似的表型，具有自我更新和多向分化能力。接种EMSCs的明胶-壳聚糖支架可提高ALF大鼠模型的存活率，改善肝功能和病理状况。此外，移植的EMSCs可分泌旁分泌因子，促进肝细胞再生、靶向迁移，并响应肝脏微环境转分化为HLCs，进而修复或替代受损肝细胞。与成熟肝细胞相似，由EMSCs产生的HLCs具有表达特异性肝标志物、储存糖原和产生尿素的功能。
这些结果证实了EMSCs在急性肝衰竭治疗中的可行性。据我们所知，这是首次将EMSCs用于肝病治疗。EMSCs有望成为肝组织工程中一种新型且有前景的细胞来源。
