Prostacyclin-producing human mesenchymal cells target H19 lncRNA to augment endogenous progenitor function in hindlimb ischaemia

被引：31

作者：

Deng, Yuxiao ^{[1
]}

Yang, Zhongwei ^{[1
]}

Terry, Toya ^{[1
]}

Pan, Su ^{[1
]}

Woodside, Darren G. ^{[1
]}

Wang, Jingxiong ^{[1
]}

Ruan, Kehe ^{[2
]}

Willerson, James T. ^{[1
]}

Dixon, Richard A. F. ^{[1
]}

Liu, Qi ^{[1
]}

机构：

[1] St Lukes Episcopal Hosp, Texas Heart Inst, Wafic Said Mol Cardiol Res Lab, POB 20345,MC 2-255, Houston, TX 77225 USA

[2] Univ Houston, Dept Pharmacol & Pharmaceut Sci, 552 Sci & Res Bldg 2, Houston, TX 77204 USA

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

关键词：

SKELETAL-MUSCLE; BONE-MARROW; NONCODING RNA; BLOOD-FLOW; SYNTHASE; GENE; TRANSPLANTATION; CYCLOOXYGENASE; BIOSYNTHESIS; MICRORNAS;

D O I：

10.1038/ncomms11276

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 (PGI(2)-hMSCs). We show that PGI(2)-hMSCs facilitate perfusion recovery and enhance running capability as compared with control hMSCs or iloprost (a stable PGI(2) analogue). Transplanted PGI(2)-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 PGI(2)-hMSC-associated survival and proliferation of host progenitor cells under hypoxic conditions. Together, our data reveal the novel ability of PGI(2)-hMSCs to stimulate host regenerative processes and improve physical function by regulating long noncoding RNA in resident progenitor cells.

引用

页数：12

共 35 条

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