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

Yuxiao Deng, Zhongwei Yang, Toya Terry, Su Pan, Darren G. Woodside, Jingxiong Wang, Kehe Ruan, James T. Willerson, Richard A. F. Dixon and Qi Liu ()
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Yuxiao Deng: Wafic Said Molecular Cardiology Research Laboratory, Texas Heart Institute
Zhongwei Yang: Wafic Said Molecular Cardiology Research Laboratory, Texas Heart Institute
Toya Terry: Wafic Said Molecular Cardiology Research Laboratory, Texas Heart Institute
Su Pan: Wafic Said Molecular Cardiology Research Laboratory, Texas Heart Institute
Darren G. Woodside: Wafic Said Molecular Cardiology Research Laboratory, Texas Heart Institute
Jingxiong Wang: Wafic Said Molecular Cardiology Research Laboratory, Texas Heart Institute
Kehe Ruan: University of Houston
James T. Willerson: Wafic Said Molecular Cardiology Research Laboratory, Texas Heart Institute
Richard A. F. Dixon: Wafic Said Molecular Cardiology Research Laboratory, Texas Heart Institute
Qi Liu: Wafic Said Molecular Cardiology Research Laboratory, Texas Heart Institute

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: Abstract 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.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11276

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DOI: 10.1038/ncomms11276

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