title: Prostacyclin-producing human mesenchymal cells target H19 lncRNA to augment endogenous progenitor function in hindlimb ischaemia.
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.
authors.affiliation: Wafic Said Molecular Cardiology Research Laboratory, Texas Heart Institute, P.O. Box 20345, MC 2-255, Houston, Texas 77225-0345, USA.
authors.forename: Yuxiao
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Wafic Said Molecular Cardiology Research Laboratory, Texas Heart Institute, P.O. Box 20345, MC 2-255, Houston, Texas 77225-0345, USA.
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Wafic Said Molecular Cardiology Research Laboratory, Texas Heart Institute, P.O. Box 20345, MC 2-255, Houston, Texas 77225-0345, USA.
authors.forename: Toya
authors.initials: T
authors.lastname: Terry
authors.affiliation: Wafic Said Molecular Cardiology Research Laboratory, Texas Heart Institute, P.O. Box 20345, MC 2-255, Houston, Texas 77225-0345, USA.
authors.forename: Su
authors.initials: S
authors.lastname: Pan
authors.affiliation: Wafic Said Molecular Cardiology Research Laboratory, Texas Heart Institute, P.O. Box 20345, MC 2-255, Houston, Texas 77225-0345, USA.
authors.forename: Darren G
authors.initials: DG
authors.lastname: Woodside
authors.affiliation: Wafic Said Molecular Cardiology Research Laboratory, Texas Heart Institute, P.O. Box 20345, MC 2-255, Houston, Texas 77225-0345, USA.
authors.forename: Jingxiong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, 552 Science and Research Building 2, Houston, Texas 77204-5037, USA.
authors.forename: Kehe
authors.initials: K
authors.lastname: Ruan
authors.affiliation: Wafic Said Molecular Cardiology Research Laboratory, Texas Heart Institute, P.O. Box 20345, MC 2-255, Houston, Texas 77225-0345, USA.
authors.forename: James T
authors.initials: JT
authors.lastname: Willerson
authors.affiliation: Wafic Said Molecular Cardiology Research Laboratory, Texas Heart Institute, P.O. Box 20345, MC 2-255, Houston, Texas 77225-0345, USA.
authors.forename: Richard A F
authors.initials: RA
authors.lastname: Dixon
authors.affiliation: Wafic Said Molecular Cardiology Research Laboratory, Texas Heart Institute, P.O. Box 20345, MC 2-255, Houston, Texas 77225-0345, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism*; D057809:HEK293 Cells; D006614:Hindlimb / Q000098:blood supply*; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D007511:Ischemia / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009043:Motor Activity; D062085:RNA, Long Noncoding / Q000235:genetics*; D012420:Running; D014183:Transplantation, Heterologous; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D014665:Vasodilator Agents; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D016285:Iloprost