| Activation of diverse signaling pathways by ex-vivo delivery of multiple cytokines for myocardial repair. | |
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MedLine Citation:
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PMID: 22873203 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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We tested the hypothesis that simultaneous transgenic overexpression of a select quartet of growth factors activates diverse signaling pathways for mobilization and participation of various stem/progenitor cells for cardiogenesis in the infarcted heart. Human IGF-1, VEGF, SDF-1α and HGF plasmids were synthesized and transfected into skeletal myoblasts (SMs) from young male wild type or GFP<sup>+</sup> transgenic rats (<sup>Trans</sup>SMs). Overexpression of growth factors in transfected SM (<sup>Trans</sup>SM) was confirmed by RT-PCR, Western blotting and fluorescence immunostaining. Using our custom-made growth factor array and Western blotting, multiple angiogenic and pro-survival factors were detected in <sup>Trans</sup>SMs including SFRP-1,2,4,5, MMP-3 &9, connexin-43, netrin-1, Nos-2, Wnt-3, Akt, MAPK42/44, Stat3, NFκB, HIF-1α, and PKC. Conditioned medium (CM) from TransSMs was cytoprotective for cardiomyocytes under anoxia (<i>p</i><0.01 <i>vs</i> CM from <sup>Nat</sup>SMs), promoted higher trans-well migration of human umbilical cord vein endothelial cells (223.3±1.8; <i>p</i><0.01) and in vitro tube formation (47.8±1.9, <i>p</i><0.01). Intramyocardial transplantation of 1.5x10<sup>6</sup> TransSMs (groups-3) in a rat model of acute myocardial infarction induced extensive mobilization of cMet<sup>+</sup>, ckit<sup>+</sup>, ckit<sup>+</sup>/GATA<sup>+</sup>, CXCR4<sup>+</sup>, CD44<sup>+</sup>, CD31<sup>+</sup>, and CD59<sup>+</sup> cells into the infarcted heart on day 7 and improved integration of <sup>Trans</sup>SMs in the heart (<i>p</i><0.05 <i>vs</i> group-2). Extensive neomyogenesis and angiogenesis in groups-3 (<i>p</i><0.01 <i>vs</i> group-2) with resultant attenuation of infarct size (<i>p</i><0.01 <i>vs</i> group-2) and improvement in global heart function (<i>p</i><0.01 <i>vs</i> group-2) was observed at 8 weeks.In conclusion, simultaneous activation of diverse signaling pathways by overexpression of multiple growth factors caused massive mobilization and homing of stem/progenitor cells from peripheral circulation, the bone marrow and the heart for accelerated repair of the infarcted myocardium. |
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Authors:
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Mikhail Konoplyannikov; Khawaja Haider; Vien Khach Lai; Rafeeq Ph Ahmed; Shujia Jinag; Muhammad Ashraf |
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2705583 - Beat-to-beat regulation of left ventricular function in the intact cardiovascular system. 141883 - The evaluation of left ventricular function by echocardiography. 18357503 - Country of birth and survival after a first myocardial infarction in stockholm, sweden. |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-8-8 |
Journal Detail:
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Title: Stem cells and development Volume: - ISSN: 1557-8534 ISO Abbreviation: Stem Cells Dev. Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-8-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101197107 Medline TA: Stem Cells Dev Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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University of Cincinnati, PAthology, Cincinnati, Ohio, United States; mkonopl@mail.ru. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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