CD73 Expression on Mesenchymal Stem Cells Dictates the Reparative Properties via Its Anti-Inflammatory Activity
CD73 Expression on Mesenchymal Stem Cells Dictates the Reparative Properties via Its Anti-Inflammatory Activity
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间充质干细胞上的 CD73 表达通过其抗炎活性决定修复特性
DOI：
10.1155/2019/8717694
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发表时间：
2019-01-01
影响因子：
4.3
通讯作者：
Deng, Xiaoming
中科院分区：
文献类型：
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作者：
Tan, Kezhe;Zhu, Hongtao;Deng, Xiaoming
骨髓间充质干细胞（MSC）不是通用的，在体内局部环境和体外分离培养后可能发生动态变化。在这里，我们证明了来源于鼠心包脂肪组织（pMSC）的MSC构成了两个群体，其区别在于CD 73表达水平（称为CD 73高和CD 73低pMSC）。将两种类型的细胞移植到心肌梗死（MI）后的小鼠心脏中，结果显示，与PBS对照和CD 73 low pMSC相比，CD 73 high pMSC优先带来结构和功能修复。此外，CD 73 high pMSC在体内移植和与腹腔巨噬细胞体外共培养后5天通过减弱CCR 2+巨噬细胞浸润和上调几种抗炎基因而显示出显著的抗炎活性。在与来自CD 73敲除小鼠（CD 73 −/−）的pMSC的共培养实验中未观察到免疫调节作用，但A2 b受体拮抗剂PSB 603的预处理部分阻断了免疫调节作用。这些结果突出了CD 73表达的异质性，这可能与其催化产物对局部免疫应答的调节有关，从而为在基于干细胞的治疗中使用不同来源的供体细胞时再生结果的不一致性提供了可能的解释。
Mesenchymal stem cells (MSC) are not universal and may be subject to dynamic changes upon local milieus in vivo and after isolation and cultivation in vitro. Here, we demonstrate that MSC derived from murine pericardial adipose tissue (pMSC) constitute two cohorts of population distinguished by the level of CD73 expression (termed as CD73high and CD73low pMSC). Transplantation of two types of cells into mouse hearts after myocardial infarction (MI) revealed that the CD73high pMSC preferentially brought about structural and functional repair in comparison to the PBS control and CD73low pMSC. Furthermore, the CD73high pMSC displayed a pronounced anti-inflammatory activity by attenuating CCR2+ macrophage infiltration and upregulating several anti-inflammatory genes 5 days after in vivo transplantation and ex vivo cocultivation with peritoneal macrophages. The immunomodulatory effect was not seen in cocultivation experiments with pMSC derived from CD73 knockout mice (CD73−/−) but was partially blocked by pretreatment of the A2b receptor antagonist, PSB603. The results highlight a heterogeneity of the CD73 expression that may be related to its catalytic products on the modulation of the local immune response and thus provide a possible explanation to the inconsistency of the regenerative results when different sources of donor cells were used in stem cell-based therapy.