Comparison of the biological and functional characteristics of mesenchymal stem cells from intrahepatic and identical bone marrow
Comparison of the biological and functional characteristics of mesenchymal stem cells from intrahepatic and identical bone marrow
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肝内间充质干细胞与同种骨髓间充质干细胞生物学和功能特性的比较
DOI：
10.1016/j.scr.2021.102477
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发表时间：
2021-08-01
影响因子：
1.2
通讯作者：
Bai，Lianhua
中科院分区：
文献类型：
--
作者：
Lai，Jiejuan;Jiang，Shifang;Bai，Lianhua
在我们先前的工作中，我们的研究小组表征了一群称为MLpvNG 2+细胞的肝源性间充质干细胞（MSC）。在本研究中，我们使用体外（条件培养基）和体内（良好设置的二乙基亚硝胺（DEN）诱导的肝纤维化/肝硬化小鼠模型）程序比较了幼稚MLpvNG 2细胞与相同骨髓来源的MSC（niBM-MSC）的生物学和功能特征。肝内来源的中胚层MLpvNG 2+细胞表现出一些生物学特性（例如，一组表面标志物）。在响应病理条件的信号，如肝纤维化/坏死信号时，MLpvNG 2+细胞显示出更高的存活率，并有利于分化为ALB（+）和G6 Pc（+）肝细胞，而mIBM-MSC主要分化为CK/KRT 19（+）胆管细胞。我们将C/EBPα/β表达鉴定为区分这两个MSC群体的生物学特征，其中MLpvNG 2+细胞可能受C/EBPβ转录信号传导调节，而niBM-MSC可能受C/EBPα转录信号传导控制。值得注意的是，尽管C/EBPα和C/EBPβ转录信号分别调节肝细胞和胆管细胞的命运，但据我们所知，这些蛋白在MLpvNG 2+细胞中的表达在本研究中首次报道。我们用体外和体内的抗C/EBP中和抗体（Abs）来确定这些蛋白的功能特性。我们的结论是，这两个群体的MSC的生物学特性取决于他们的差异C/EBPα/β表达模式。
In our privious work, our reseach group characterized a population of hepatic-sourced mesenchymal stem cells (MSCs) called MLpvNG2+cells. In the present study, we compared the biological and functional characteristics of naïve MLpvNG2 cells with identical bone marrow-derived MSCs (niBM-MSCs) usingin vitro(conditioned media) andin vivo(a well-set diethylnitrosamine (DEN)-induced liver fibrotic/cirrhotic murine model) procedures. The intrahepatic-sourced mesodermal MLpvNG2+cells exhibited some biological characteristics (e.g., a set of surface markers) similar to those of extrahepatic niBM-MSCs. In responsed to signals of pathological conditions, such as singals of fibrotic/cirrhotic liver, MLpvNG2+cells showed higher survival and favored differentiation into ALB(+) and G6Pc(+) hepatocytes, whereas niBM-MSCs predominantly differentiated into CK/KRT19(+) cholangiocytes. We identified C/EBPα/β expression as a biological characteristic differentiating these two populations of MSCs, wherein MLpvNG2+cells are likely regulated by C/EBPβ transcriptional signaling, whereas niBM-MSCs are likely controlled by C/EBPα transcriptional signaling. Notably, although C/EBPα and C/EBPβ transcriptional signaling regulate hepatocyte and cholangiocyte fate, respectively, the expression of these proteins in MLpvNG2+cells is, to our knowledge, reported for the first time in the present study. We used anti-C/EBP neutralizing antibodies (Abs) bothin vitroandin vivoto determine the functional characteristics of these proteins. We conclude that the biological characteristics of these two populations of MSCs depend on their differential C/EBPα/β expression patterns.