Prostacyclin-producing human mesenchymal cells target H19 lncRNA to augment endogenous progenitor function in hindlimb ischaemia.
Prostacyclin-producing human mesenchymal cells target H19 lncRNA to augment endogenous progenitor function in hindlimb ischaemia.
复制标题
DOI：
10.1038/ncomms11276
复制
发表时间：
2016-04-15
影响因子：
16.6
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Deng Y;Yang Z;Terry T;Pan S;Woodside DG;Wang J;Ruan K;Willerson JT;Dixon RA;Liu Q
促进人类间充质干细胞（hMSC）治疗的旁分泌效应可能有助于改善患者的预后。在这里，我们开发了一种创新的策略，以增强hMSCs的旁分泌作用。在小鼠后肢缺血模型中，我们研究了hMSCs的作用，其中引入了一种新的三重催化酶以稳定地产生前列环素（PGI 2-hMSCs）。我们表明，PGI 2-hMSCs促进灌注恢复和提高运行能力相比，控制hMSCs或伊洛前列素（一种稳定的PGI 2类似物）。移植的PGI 2-hMSC不长期掺入宿主组织，而是以旁分泌方式介导宿主再生和肌肉质量增加。在机制上，这涉及长的非编码RNA H19在促进PGI 2-hMSC相关的宿主祖细胞在缺氧条件下的存活和增殖。总之，我们的数据揭示了PGI 2-hMSCs通过调节常驻祖细胞中的长非编码RNA来刺激宿主再生过程和改善身体功能的新能力。 表达旁分泌因子的人间充质干细胞（hMSC）移植后可能会增强治疗效果。在这里，作者表明，在小鼠后肢缺血模型中，稳定表达前列环素的hMSC增强宿主再生和肌肉质量增加，由长的非编码RNA H19介导。
Promoting the paracrine effects of human mesenchymal stem cell (hMSC) therapy may contribute to improvements in patient outcomes. Here we develop an innovative strategy to enhance the paracrine effects of hMSCs. In a mouse hindlimb ischaemia model, we examine the effects of hMSCs in which a novel triple-catalytic enzyme is introduced to stably produce prostacyclin (PGI2-hMSCs). We show that PGI2-hMSCs facilitate perfusion recovery and enhance running capability as compared with control hMSCs or iloprost (a stable PGI2 analogue). Transplanted PGI2-hMSCs do not incorporate long term into host tissue, but rather they mediate host regeneration and muscle mass gain in a paracrine manner. Mechanistically, this involves long noncoding RNA H19 in promoting PGI2-hMSC-associated survival and proliferation of host progenitor cells under hypoxic conditions. Together, our data reveal the novel ability of PGI2-hMSCs to stimulate host regenerative processes and improve physical function by regulating long noncoding RNA in resident progenitor cells. Human mesenchymal stem cells (hMSC) expressing paracrine factors may enhance therapeutic benefits when transplanted. Here, the authors show that hMSCs stably expressing prostacyclin enhance host regeneration and muscle mass gain in a mouse hindlimb ischaemia model, mediated by the long noncoding RNA H19.