人类小唾液腺上皮祖细胞在肝再生中的治疗潜力  

Therapeutic potential of human minor salivary gland epithelial progenitor cells in liver regeneration  

Authors: Chen Zhang, Yan Li, Xiangyu Zhang, Lei Liu, Haizhou Tong, TingJu Han, Wandi Li, Xiaolei Jin, Ningbei Yin, Tao Song, Haidong Li, Juan Zhi, Zhenmin Zhao, Lin Lu  

摘要:  

肝病是影响数百万人的严重问题，患病率持续上升。干细胞治疗已成为治疗肝功能障碍的一种有前景的方法。我们先前报道了人类小唾液腺间充质干细胞（hMSGMSCs），其具有高度自我更新和多向分化能力。在本研究中，分离并表征了具有自我再生和肝分化潜力的角质形成细胞样细胞，命名为人类小唾液腺上皮祖细胞（hMSGEpiPCs）。hMSGEpiPCs通过微创口腔内切口容易获得；它们表达上皮祖细胞/干细胞和其他组织干细胞标志物，如CD29、CD49f、细胞角蛋白、ABCG2、PLET1、唾液腺上皮细胞标志物CD44和CD166，以及Wnt靶基因LGR5和LGR6。这些细胞在体外被诱导为功能性肝细胞，表达肝脏相关标志物ALB、CYP3A4、AAT和CK18。在体内移植后，它们改善了由四氯化碳（CCl4）注射引起的严重急性肝损伤小鼠的肝功能。在三分之二部分肝切除小鼠模型中，移植的细胞存活至少4周并表现出肝分化潜力。这些发现表明，hMSGEpiPCs具有作为肝病细胞治疗、生理和毒理学研究以及再生医学的潜力。  

Abstract:

Liver disease is a serious problem affecting millions of people with continually increasing prevalence. Stem cell therapy has become a promising treatment for liver dysfunction. We previously reported on human minor salivary gland mesenchymal stem cells (hMSGMSCs), which are highly selfrenewable with multipotent differentiation capability. In this study, keratinocytelike cells with selfregeneration and hepatic differentiation potential were isolated and characterized, and named human minor salivary gland epithelial progenitor cells (hMSGEpiPCs). hMSGEpiPCs were easily obtained via minor intraoral incision; they expressed epithelial progenitor/stem cell and other tissue stem cell markers such as CD29, CD49f, cytokeratins, ABCG2, PLET1, salivary epithelial cell markers CD44 and CD166, and the Wnt target related gene LGR5 and LGR6. The cells were induced into functional hepatocytes in vitro which expressed liverassociated markers ALB, CYP3A4, AAT, and CK18. Upon transplantation in vivo, they ameliorated severe acute liver damage in SCID mice caused by carbon tetrachloride (CCl4) injection. In a twothirds partial hepatectomy mouse model, the transplanted cells survived at least 4 weeks and exhibited hepatic potential. These findings demonstrate that hMSGEpiPCs have potential as a cellular therapy basis for hepatic diseases, physiological and toxicology studies and regenerative medicine.