NKX6.1协同PDX1诱导人胎肝间充质干细胞分化为胰岛B样细胞

目的探讨NKX6.1对PDX1诱导人胎肝间充质干细胞(fetal liver-derived mesenchymal stem cells,FL-MSCs)向胰岛B细胞分化的协同作用及可能机制,以获取足够用于移植的胰岛B样细胞。方法构建含PDX1与NKX6.1双基因的重组腺病毒载体,用该载体感染FL-MSCs并联合相应的细胞因子分步诱导,检测诱导后的细胞中PDX1和NKX6.1基因以及NGN3、NeuroD1/Beta2、MafA因子和胰岛素等多种胰腺B细胞相关分子的表达情况。结果腺病毒载体转染24h后FL-MSCs细胞即开始表达PDX1与NKX6.1基因,检测显示诱导后的细胞先后开始表达NGN3、NeuroD1和MafA等因子,持续稳定表达胰岛素等B细胞相关分子;且这些分子表达存在时序性。结论PDX1与NKX6.1联合细胞因子在体外能有效诱导FL-MSCs分化为胰岛B样细胞;可能是通过先后活化的NGN3、NeuroD1和MafA等转录因子,限定细胞向内分泌前体细胞、进一步向B内分泌前体细胞、B细胞分化发育。

NKX6.1 combined with PDX1 induces mesenchymal stem cell differentiation into B-like cells

Objective To study the synergistic effect of NKX6.1 and PDX1 in inducing differentiation of fetal liver-derived mesenchymal stem cells(FL-MSCs) into the pancreatic B cells and to explore the underlying mechanisms,so as to obtain enough islet-like body for transplantation.Methods Recombinant adenovirus vector harboring both PDX1 and NKX6.1 genes was constructed,and the vector was used to infect FL-MSCs.Then a series of cytokines were used to induce the differentiation of infected FL-MSCs into pancreatic B ce...