Stem cell-based delivery of Hypoxamir-210 to the infarcted heart: implications on stem cell survival and preservation of infarcted heart function
This study seeks to test our hypothesis that transgenic induction of miR-210 in mesenchymal stem cells (MSC) simulates the pro-survival effects of ischemic preconditioning (IPC) and that engraftment of PC MSC helps in the functional recovery of ischemic heart by miR-210 transfer to host cardiomyocyt...
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| Veröffentlicht in: | Journal of molecular medicine (Berlin, Germany) Germany), 2012-09, Vol.90 (9), p.997-1010 |
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| creator | Kim, Ha Won Jiang, Shujia Ashraf, Muhammad Haider, Khawaja Husnain |
| description | This study seeks to test our hypothesis that transgenic induction of miR-210 in mesenchymal stem cells (MSC) simulates the pro-survival effects of ischemic preconditioning (IPC) and that engraftment of
PC
MSC helps in the functional recovery of ischemic heart by miR-210 transfer to host cardiomyocytes through gap junctions. miR-210 expression in MSC was achieved by IPC or nanoparticle-based transfection of miR-210 plasmid (
miR
MSC) and functional recovery of the infarcted heart of rat transplanted with
PC
MSC or
miR
MSC was evaluated. Both
PC
MSC and
miR
MSC showed higher survival under lethal anoxia as compared to
non-PC
MSC and scramble-transfected MSC (
Sc
MSC) controls with concomitantly lower CASP8AP2 expression. Similarly, both
PC
MSC and
miR
MSC survived better and accelerated functional recovery of ischemic heart post-transplantation. To validate our hypothesis that MSC deliver miR-210 to host cardiomyocytes, in vitro co-culture between cardiomyocytes and
PC
MSC or
miR
MSC (using
non-PC
MSC or
Sc
MSC as controls) showed co-localization of miR-210 with gap-junctional connexin-43. miR-210 transfer to cardiomyocytes was blocked by heptanol pretreatment. Moreover, higher survival of cardiomyocytes co-cultured with
PC
MSC was observed with concomitant expression of CASP8AP2 as compared to cardiomyocytes co-cultured with
non-PC
MSC thus suggesting that miR-210 was translocated from MSC to protect host cardiomyocytes. Induction of miR-210 in MSC promoted their survival post-engraftment in the infarcted heart. Moreover, direct transfer of pro-survival miR-210 from
miR
MSC to host cardiomyocytes led to functional recovery of the ischemic heart. |
| doi_str_mv | 10.1007/s00109-012-0920-1 |
| format | Article |
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PC
MSC helps in the functional recovery of ischemic heart by miR-210 transfer to host cardiomyocytes through gap junctions. miR-210 expression in MSC was achieved by IPC or nanoparticle-based transfection of miR-210 plasmid (
miR
MSC) and functional recovery of the infarcted heart of rat transplanted with
PC
MSC or
miR
MSC was evaluated. Both
PC
MSC and
miR
MSC showed higher survival under lethal anoxia as compared to
non-PC
MSC and scramble-transfected MSC (
Sc
MSC) controls with concomitantly lower CASP8AP2 expression. Similarly, both
PC
MSC and
miR
MSC survived better and accelerated functional recovery of ischemic heart post-transplantation. To validate our hypothesis that MSC deliver miR-210 to host cardiomyocytes, in vitro co-culture between cardiomyocytes and
PC
MSC or
miR
MSC (using
non-PC
MSC or
Sc
MSC as controls) showed co-localization of miR-210 with gap-junctional connexin-43. miR-210 transfer to cardiomyocytes was blocked by heptanol pretreatment. Moreover, higher survival of cardiomyocytes co-cultured with
PC
MSC was observed with concomitant expression of CASP8AP2 as compared to cardiomyocytes co-cultured with
non-PC
MSC thus suggesting that miR-210 was translocated from MSC to protect host cardiomyocytes. Induction of miR-210 in MSC promoted their survival post-engraftment in the infarcted heart. Moreover, direct transfer of pro-survival miR-210 from
miR
MSC to host cardiomyocytes led to functional recovery of the ischemic heart.</description><identifier>ISSN: 0946-2716</identifier><identifier>EISSN: 1432-1440</identifier><identifier>DOI: 10.1007/s00109-012-0920-1</identifier><identifier>PMID: 22648522</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Animals ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cardiology. Vascular system ; Cell Survival ; Cells, Cultured ; Coculture Techniques ; Coronary heart disease ; Female ; Gap Junctions - metabolism ; Gene Transfer Techniques ; General aspects ; Heart ; Heart - physiopathology ; Human Genetics ; Internal Medicine ; Male ; Medical sciences ; Mesenchymal Stem Cell Transplantation - methods ; Mesenchymal Stromal Cells - cytology ; Mesenchymal Stromal Cells - metabolism ; MicroRNAs - administration & dosage ; MicroRNAs - genetics ; MicroRNAs - metabolism ; MicroRNAs - therapeutic use ; Molecular Medicine ; Myocardial Infarction - genetics ; Myocardial Infarction - physiopathology ; Myocardial Infarction - surgery ; Myocardial Infarction - therapy ; Myocytes, Cardiac - cytology ; Myocytes, Cardiac - metabolism ; Original Article ; Rats ; Rats, Inbred F344 ; Up-Regulation</subject><ispartof>Journal of molecular medicine (Berlin, Germany), 2012-09, Vol.90 (9), p.997-1010</ispartof><rights>Springer-Verlag 2012</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c500t-524d84315e4c29071dc201f97eec1b22298bfa1a4bf93d74e7c4261f8929b1493</citedby><cites>FETCH-LOGICAL-c500t-524d84315e4c29071dc201f97eec1b22298bfa1a4bf93d74e7c4261f8929b1493</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00109-012-0920-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00109-012-0920-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26270478$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22648522$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Ha Won</creatorcontrib><creatorcontrib>Jiang, Shujia</creatorcontrib><creatorcontrib>Ashraf, Muhammad</creatorcontrib><creatorcontrib>Haider, Khawaja Husnain</creatorcontrib><title>Stem cell-based delivery of Hypoxamir-210 to the infarcted heart: implications on stem cell survival and preservation of infarcted heart function</title><title>Journal of molecular medicine (Berlin, Germany)</title><addtitle>J Mol Med</addtitle><addtitle>J Mol Med (Berl)</addtitle><description>This study seeks to test our hypothesis that transgenic induction of miR-210 in mesenchymal stem cells (MSC) simulates the pro-survival effects of ischemic preconditioning (IPC) and that engraftment of
PC
MSC helps in the functional recovery of ischemic heart by miR-210 transfer to host cardiomyocytes through gap junctions. miR-210 expression in MSC was achieved by IPC or nanoparticle-based transfection of miR-210 plasmid (
miR
MSC) and functional recovery of the infarcted heart of rat transplanted with
PC
MSC or
miR
MSC was evaluated. Both
PC
MSC and
miR
MSC showed higher survival under lethal anoxia as compared to
non-PC
MSC and scramble-transfected MSC (
Sc
MSC) controls with concomitantly lower CASP8AP2 expression. Similarly, both
PC
MSC and
miR
MSC survived better and accelerated functional recovery of ischemic heart post-transplantation. To validate our hypothesis that MSC deliver miR-210 to host cardiomyocytes, in vitro co-culture between cardiomyocytes and
PC
MSC or
miR
MSC (using
non-PC
MSC or
Sc
MSC as controls) showed co-localization of miR-210 with gap-junctional connexin-43. miR-210 transfer to cardiomyocytes was blocked by heptanol pretreatment. Moreover, higher survival of cardiomyocytes co-cultured with
PC
MSC was observed with concomitant expression of CASP8AP2 as compared to cardiomyocytes co-cultured with
non-PC
MSC thus suggesting that miR-210 was translocated from MSC to protect host cardiomyocytes. Induction of miR-210 in MSC promoted their survival post-engraftment in the infarcted heart. Moreover, direct transfer of pro-survival miR-210 from
miR
MSC to host cardiomyocytes led to functional recovery of the ischemic heart.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cardiology. Vascular system</subject><subject>Cell Survival</subject><subject>Cells, Cultured</subject><subject>Coculture Techniques</subject><subject>Coronary heart disease</subject><subject>Female</subject><subject>Gap Junctions - metabolism</subject><subject>Gene Transfer Techniques</subject><subject>General aspects</subject><subject>Heart</subject><subject>Heart - physiopathology</subject><subject>Human Genetics</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mesenchymal Stem Cell Transplantation - methods</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Mesenchymal Stromal Cells - metabolism</subject><subject>MicroRNAs - administration & dosage</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>MicroRNAs - therapeutic use</subject><subject>Molecular Medicine</subject><subject>Myocardial Infarction - genetics</subject><subject>Myocardial Infarction - physiopathology</subject><subject>Myocardial Infarction - surgery</subject><subject>Myocardial Infarction - therapy</subject><subject>Myocytes, Cardiac - cytology</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Original Article</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Up-Regulation</subject><issn>0946-2716</issn><issn>1432-1440</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kcFu1DAQhiMEokvhAbggSwiJi8EzceKYQyVUAUWqxAE4W45jd10l9mInEfsYvDEJuy2lEicf_m8-z-gviufA3gBj4m1mDJikDJAyiYzCg2IDvEQKnLOHxYZJXlMUUJ8UT3K-XmhRSf64OEGseVMhbopfX0c7EGP7nrY62450tvezTXsSHbnY7-JPPfhEERgZIxm3lvjgdDLjgm6tTuM74odd740efQyZxEDyjZHkKc1-1j3RoSO7ZLNN8x9uld_zEDcFs2ZPi0dO99k-O76nxfePH76dX9DLL58-n7-_pKZibKQV8q7hJVSWG5RMQGeQgZPCWgMtIsqmdRo0b50sO8GtMBxrcI1E2QKX5WlxdvDupnawnbFhTLpXu-QHnfYqaq_-TYLfqqs4q5JjySUugtdHQYo_JptHNfi83q2DjVNWwEpegeCwoi_voddxSmE5b6UENsAqsVBwoEyKOSfrbpcBptbC1aFwtRSu1sIVLDMv7l5xO3HT8AK8OgI6G927pIPx-S9Xo2BcNAuHBy4vUbiy6e6K__v9N9lcxKo</recordid><startdate>20120901</startdate><enddate>20120901</enddate><creator>Kim, Ha Won</creator><creator>Jiang, Shujia</creator><creator>Ashraf, Muhammad</creator><creator>Haider, Khawaja Husnain</creator><general>Springer-Verlag</general><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20120901</creationdate><title>Stem cell-based delivery of Hypoxamir-210 to the infarcted heart: implications on stem cell survival and preservation of infarcted heart function</title><author>Kim, Ha Won ; Jiang, Shujia ; Ashraf, Muhammad ; Haider, Khawaja Husnain</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c500t-524d84315e4c29071dc201f97eec1b22298bfa1a4bf93d74e7c4261f8929b1493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cardiology. Vascular system</topic><topic>Cell Survival</topic><topic>Cells, Cultured</topic><topic>Coculture Techniques</topic><topic>Coronary heart disease</topic><topic>Female</topic><topic>Gap Junctions - metabolism</topic><topic>Gene Transfer Techniques</topic><topic>General aspects</topic><topic>Heart</topic><topic>Heart - physiopathology</topic><topic>Human Genetics</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mesenchymal Stem Cell Transplantation - methods</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Mesenchymal Stromal Cells - metabolism</topic><topic>MicroRNAs - administration & dosage</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>MicroRNAs - therapeutic use</topic><topic>Molecular Medicine</topic><topic>Myocardial Infarction - genetics</topic><topic>Myocardial Infarction - physiopathology</topic><topic>Myocardial Infarction - surgery</topic><topic>Myocardial Infarction - therapy</topic><topic>Myocytes, Cardiac - cytology</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Original Article</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Ha Won</creatorcontrib><creatorcontrib>Jiang, Shujia</creatorcontrib><creatorcontrib>Ashraf, Muhammad</creatorcontrib><creatorcontrib>Haider, Khawaja Husnain</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of molecular medicine (Berlin, Germany)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Ha Won</au><au>Jiang, Shujia</au><au>Ashraf, Muhammad</au><au>Haider, Khawaja Husnain</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stem cell-based delivery of Hypoxamir-210 to the infarcted heart: implications on stem cell survival and preservation of infarcted heart function</atitle><jtitle>Journal of molecular medicine (Berlin, Germany)</jtitle><stitle>J Mol Med</stitle><addtitle>J Mol Med (Berl)</addtitle><date>2012-09-01</date><risdate>2012</risdate><volume>90</volume><issue>9</issue><spage>997</spage><epage>1010</epage><pages>997-1010</pages><issn>0946-2716</issn><eissn>1432-1440</eissn><abstract>This study seeks to test our hypothesis that transgenic induction of miR-210 in mesenchymal stem cells (MSC) simulates the pro-survival effects of ischemic preconditioning (IPC) and that engraftment of
PC
MSC helps in the functional recovery of ischemic heart by miR-210 transfer to host cardiomyocytes through gap junctions. miR-210 expression in MSC was achieved by IPC or nanoparticle-based transfection of miR-210 plasmid (
miR
MSC) and functional recovery of the infarcted heart of rat transplanted with
PC
MSC or
miR
MSC was evaluated. Both
PC
MSC and
miR
MSC showed higher survival under lethal anoxia as compared to
non-PC
MSC and scramble-transfected MSC (
Sc
MSC) controls with concomitantly lower CASP8AP2 expression. Similarly, both
PC
MSC and
miR
MSC survived better and accelerated functional recovery of ischemic heart post-transplantation. To validate our hypothesis that MSC deliver miR-210 to host cardiomyocytes, in vitro co-culture between cardiomyocytes and
PC
MSC or
miR
MSC (using
non-PC
MSC or
Sc
MSC as controls) showed co-localization of miR-210 with gap-junctional connexin-43. miR-210 transfer to cardiomyocytes was blocked by heptanol pretreatment. Moreover, higher survival of cardiomyocytes co-cultured with
PC
MSC was observed with concomitant expression of CASP8AP2 as compared to cardiomyocytes co-cultured with
non-PC
MSC thus suggesting that miR-210 was translocated from MSC to protect host cardiomyocytes. Induction of miR-210 in MSC promoted their survival post-engraftment in the infarcted heart. Moreover, direct transfer of pro-survival miR-210 from
miR
MSC to host cardiomyocytes led to functional recovery of the ischemic heart.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>22648522</pmid><doi>10.1007/s00109-012-0920-1</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0946-2716 |
| ispartof | Journal of molecular medicine (Berlin, Germany), 2012-09, Vol.90 (9), p.997-1010 |
| issn | 0946-2716 1432-1440 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3423492 |
| source | MEDLINE; SpringerNature Journals |
| subjects | Animals Biological and medical sciences Biomedical and Life Sciences Biomedicine Cardiology. Vascular system Cell Survival Cells, Cultured Coculture Techniques Coronary heart disease Female Gap Junctions - metabolism Gene Transfer Techniques General aspects Heart Heart - physiopathology Human Genetics Internal Medicine Male Medical sciences Mesenchymal Stem Cell Transplantation - methods Mesenchymal Stromal Cells - cytology Mesenchymal Stromal Cells - metabolism MicroRNAs - administration & dosage MicroRNAs - genetics MicroRNAs - metabolism MicroRNAs - therapeutic use Molecular Medicine Myocardial Infarction - genetics Myocardial Infarction - physiopathology Myocardial Infarction - surgery Myocardial Infarction - therapy Myocytes, Cardiac - cytology Myocytes, Cardiac - metabolism Original Article Rats Rats, Inbred F344 Up-Regulation |
| title | Stem cell-based delivery of Hypoxamir-210 to the infarcted heart: implications on stem cell survival and preservation of infarcted heart function |
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