Intravenous injection of human multilineage-differentiating stress-enduring cells alleviates mouse severe acute pancreatitis without immunosuppressants
Intravenous injection of human multilineage-differentiating stress-enduring cells alleviates mouse severe acute pancreatitis without immunosuppressants
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DOI：
10.1007/s00595-021-02382-7
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发表时间：
2021-10-23
期刊：
影响因子：
2.5
通讯作者：
Dezawa, Mari
中科院分区：
文献类型：
--
作者：
Fukase, Masahiko;Sakata, Naoaki;Dezawa, Mari
引言我们研究了静脉注射人多系分化应激耐受（Muse）细胞，非致瘤性内源性修复干细胞已经在临床试验中使用，在没有免疫抑制剂的重症急性胰腺炎（SAP）小鼠模型的影响。方法将从间充质干细胞（MSC）中收集的人Muse细胞（1.0 × 10（5）个细胞）作为SSEA-3（+）经颈静脉注射到C57 BL/6小鼠模型中，在用牛磺胆酸盐进行SAP诱导后6 h。对照组接受生理盐水或相同数量的SSEA-3 ㈠-非Muse MSC。结果72 h时，Muse组水肿参数、F4/80（+）巨噬细胞浸润和末端脱氧核苷酸转移酶dUTP缺口末端标记阳性率最低，内源性胰腺祖细胞（CK 18（+）/Ki 67（+）细胞）增殖数最高，差异有统计学意义。酶联免疫吸附试验和定量聚合酶链反应表明，与组织保护、抗炎和抗纤维化相关的VEGF、HGF、IGF-1和MMP-2的体外产生在Muse细胞中高于非Muse MSC，特别是当细胞在SAP小鼠血清中培养时。一致地，根据蛋白质印迹法，在18 h时Muse组动物的胰腺中含有比非Muse MSC和对照组中更高量的这些因子。结论静脉注射人Muse细胞可减轻SAP急性期的水肿、炎症反应和细胞凋亡。
Introduction We examined the effect of intravenously injected human multilineage-differentiating stress-enduring (Muse) cells, non-tumorigenic endogenous reparative stem cells already used in clinical trials, on a severe acute pancreatitis (SAP) mouse model without immunosuppressants. Methods Human Muse cells (1.0 x 10(5) cells) collected from mesenchymal stem cells (MSCs) as SSEA-3(+) were injected into a C57BL/6 mouse model via the jugular vein 6 h after SAP-induction with taurocholate. The control group received saline or the same number of SSEA-3(-)-non-Muse MSCs. Results Edematous parameters, F4/80(+) macrophage infiltration and terminal deoxynucleotidyl transferase dUTP nick-end labeling positivity was the lowest and the number of proliferating endogenous pancreatic progenitors (CK18(+)/Ki67(+) cells) the highest in the Muse group among the three groups, with statistical significance, at 72 h. An enzyme-linked immunosorbent assay and quantitative polymerase chain reaction demonstrated that in vitro production of VEGF, HGF, IGF-1, and MMP-2, which are relevant to tissue protection, anti-inflammation, and anti-fibrosis, were higher in Muse cells than in non-Muse MSCs, particularly when cells were cultured in SAP mouse serum. Consistently, the pancreas of animals in the Muse group contained higher amounts of those factors according to Western blotting at 18 h than that in the non-Muse MSCs and control groups. Conclusions Intravenous injection of human Muse cells was suggested to be effective for attenuating edema, inflammation and apoptosis in the acute phase of SAP.