Macroscopic fluorescence imaging: a novel technique to monitor retention and distribution of injected microspheres in an experimental model of ischemic heart failure
The limited effectiveness of cardiac cell therapy has generated concern regarding its clinical relevance. Experimental studies show that cell retention and engraftment are low after injection into ischemic myocardium, which may restrict therapy effectiveness significantly. Surgical aspects and mecha...
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| creator | Martens, Andreas Rojas, Sebastian V Baraki, Hassina Rathert, Christian Schecker, Natalie Hernandez, Sara Rojas Schwanke, Kristin Zweigerdt, Robert Martin, Ulrich Saito, Shunsuke Haverich, Axel Kutschka, Ingo |
| description | The limited effectiveness of cardiac cell therapy has generated concern regarding its clinical relevance. Experimental studies show that cell retention and engraftment are low after injection into ischemic myocardium, which may restrict therapy effectiveness significantly. Surgical aspects and mechanical loss are suspected to be the main culprits behind this phenomenon. As current techniques of monitoring intramyocardial injections are complex and time-consuming, the aim of the study was to develop a fast and simple model to study cardiac retention and distribution following intramyocardial injections. For this purpose, our main hypothesis was that macroscopic fluorescence imaging could adequately serve as a detection method for intramyocardial injections.
A total of 20 mice underwent ligation of the left anterior descending artery (LAD) for myocardial infarction. Fluorescent microspheres with cellular dimensions were used as cell surrogates. Particles (5 × 10(5)) were injected into the infarcted area of explanted resting hearts (Ex vivo myocardial injetions EVMI, n = 10) and in vivo into beating hearts (In vivo myocardial injections IVMI, n = 10). Microsphere quantification was performed by fluorescence imaging of explanted organs. Measurements were repeated after a reduction to homogenate dilutions. Cardiac microsphere retention was 2.78 × 10(5) ± 0.31 × 10(5) in the EVMI group. In the IVMI group, cardiac retention of microspheres was significantly lower (0.74 × 10(5) ± 0.18 × 10(5); p |
| doi_str_mv | 10.1371/journal.pone.0101775 |
| format | Article |
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A total of 20 mice underwent ligation of the left anterior descending artery (LAD) for myocardial infarction. Fluorescent microspheres with cellular dimensions were used as cell surrogates. Particles (5 × 10(5)) were injected into the infarcted area of explanted resting hearts (Ex vivo myocardial injetions EVMI, n = 10) and in vivo into beating hearts (In vivo myocardial injections IVMI, n = 10). Microsphere quantification was performed by fluorescence imaging of explanted organs. Measurements were repeated after a reduction to homogenate dilutions. Cardiac microsphere retention was 2.78 × 10(5) ± 0.31 × 10(5) in the EVMI group. In the IVMI group, cardiac retention of microspheres was significantly lower (0.74 × 10(5) ± 0.18 × 10(5); p<0.05). Direct fluorescence imaging revealed venous drainage through the coronary sinus, resulting in a microsphere accumulation in the left (0.90 × 10(5) ± 0.20 × 10(5)) and the right (1.07 × 10(5) ± 0.17 × 10(5)) lung. Processing to homogenates involved further particle loss (p<0.05) in both groups.
We developed a fast and simple direct fluorescence imaging method for biodistribution analysis which enabled the quantification of fluorescent microspheres after intramyocardial delivery using macroscopic fluorescence imaging. This new technique showed massive early particle loss and venous drainage into the right atrium leading to substantial accumulation of graft particles in both lungs.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0101775</identifier><identifier>PMID: 25089764</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Accumulation ; Animals ; Atrium ; Biology and Life Sciences ; Biotechnology ; Bone marrow ; Dilution ; Disease Models, Animal ; Fluorescence ; Heart ; Heart attack ; Heart attacks ; Heart diseases ; Heart failure ; Heart Failure - complications ; Heart Failure - diagnosis ; Heart surgery ; Imaging ; Injections ; Ischemia ; Laboratory animals ; Lungs ; Medical imaging ; Medical research ; Medical schools ; Medicine and Health Sciences ; Methods ; Mice, Inbred BALB C ; Microspheres ; Molecular Imaging - methods ; Myocardial infarction ; Myocardial Ischemia - complications ; Myocardial Ischemia - diagnosis ; Myocardium ; NMR ; Nuclear magnetic resonance ; Organs ; Reference Standards ; Reproducibility of Results ; Research and Analysis Methods ; Retention ; Stem cells ; Studies ; Surgery ; Therapy ; Vascular surgery</subject><ispartof>PloS one, 2014-08, Vol.9 (8), p.e101775-e101775</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Martens et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Martens et al 2014 Martens et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-e7157ba3b440029d00a3f598476e999b28cd46c39473fa152c6fc3f2374061c53</citedby><cites>FETCH-LOGICAL-c692t-e7157ba3b440029d00a3f598476e999b28cd46c39473fa152c6fc3f2374061c53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4121070/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4121070/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25089764$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Frati, Giacomo</contributor><creatorcontrib>Martens, Andreas</creatorcontrib><creatorcontrib>Rojas, Sebastian V</creatorcontrib><creatorcontrib>Baraki, Hassina</creatorcontrib><creatorcontrib>Rathert, Christian</creatorcontrib><creatorcontrib>Schecker, Natalie</creatorcontrib><creatorcontrib>Hernandez, Sara Rojas</creatorcontrib><creatorcontrib>Schwanke, Kristin</creatorcontrib><creatorcontrib>Zweigerdt, Robert</creatorcontrib><creatorcontrib>Martin, Ulrich</creatorcontrib><creatorcontrib>Saito, Shunsuke</creatorcontrib><creatorcontrib>Haverich, Axel</creatorcontrib><creatorcontrib>Kutschka, Ingo</creatorcontrib><title>Macroscopic fluorescence imaging: a novel technique to monitor retention and distribution of injected microspheres in an experimental model of ischemic heart failure</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The limited effectiveness of cardiac cell therapy has generated concern regarding its clinical relevance. Experimental studies show that cell retention and engraftment are low after injection into ischemic myocardium, which may restrict therapy effectiveness significantly. Surgical aspects and mechanical loss are suspected to be the main culprits behind this phenomenon. As current techniques of monitoring intramyocardial injections are complex and time-consuming, the aim of the study was to develop a fast and simple model to study cardiac retention and distribution following intramyocardial injections. For this purpose, our main hypothesis was that macroscopic fluorescence imaging could adequately serve as a detection method for intramyocardial injections.
A total of 20 mice underwent ligation of the left anterior descending artery (LAD) for myocardial infarction. Fluorescent microspheres with cellular dimensions were used as cell surrogates. Particles (5 × 10(5)) were injected into the infarcted area of explanted resting hearts (Ex vivo myocardial injetions EVMI, n = 10) and in vivo into beating hearts (In vivo myocardial injections IVMI, n = 10). Microsphere quantification was performed by fluorescence imaging of explanted organs. Measurements were repeated after a reduction to homogenate dilutions. Cardiac microsphere retention was 2.78 × 10(5) ± 0.31 × 10(5) in the EVMI group. In the IVMI group, cardiac retention of microspheres was significantly lower (0.74 × 10(5) ± 0.18 × 10(5); p<0.05). Direct fluorescence imaging revealed venous drainage through the coronary sinus, resulting in a microsphere accumulation in the left (0.90 × 10(5) ± 0.20 × 10(5)) and the right (1.07 × 10(5) ± 0.17 × 10(5)) lung. Processing to homogenates involved further particle loss (p<0.05) in both groups.
We developed a fast and simple direct fluorescence imaging method for biodistribution analysis which enabled the quantification of fluorescent microspheres after intramyocardial delivery using macroscopic fluorescence imaging. This new technique showed massive early particle loss and venous drainage into the right atrium leading to substantial accumulation of graft particles in both lungs.</description><subject>Accumulation</subject><subject>Animals</subject><subject>Atrium</subject><subject>Biology and Life Sciences</subject><subject>Biotechnology</subject><subject>Bone marrow</subject><subject>Dilution</subject><subject>Disease Models, Animal</subject><subject>Fluorescence</subject><subject>Heart</subject><subject>Heart attack</subject><subject>Heart attacks</subject><subject>Heart diseases</subject><subject>Heart failure</subject><subject>Heart Failure - complications</subject><subject>Heart Failure - diagnosis</subject><subject>Heart surgery</subject><subject>Imaging</subject><subject>Injections</subject><subject>Ischemia</subject><subject>Laboratory animals</subject><subject>Lungs</subject><subject>Medical imaging</subject><subject>Medical research</subject><subject>Medical schools</subject><subject>Medicine and Health Sciences</subject><subject>Methods</subject><subject>Mice, Inbred BALB C</subject><subject>Microspheres</subject><subject>Molecular Imaging - methods</subject><subject>Myocardial infarction</subject><subject>Myocardial Ischemia - complications</subject><subject>Myocardial Ischemia - diagnosis</subject><subject>Myocardium</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Organs</subject><subject>Reference Standards</subject><subject>Reproducibility of Results</subject><subject>Research and Analysis Methods</subject><subject>Retention</subject><subject>Stem cells</subject><subject>Studies</subject><subject>Surgery</subject><subject>Therapy</subject><subject>Vascular 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fluorescence imaging: a novel technique to monitor retention and distribution of injected microspheres in an experimental model of ischemic heart failure</title><author>Martens, Andreas ; Rojas, Sebastian V ; Baraki, Hassina ; Rathert, Christian ; Schecker, Natalie ; Hernandez, Sara Rojas ; Schwanke, Kristin ; Zweigerdt, Robert ; Martin, Ulrich ; Saito, Shunsuke ; Haverich, Axel ; Kutschka, Ingo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-e7157ba3b440029d00a3f598476e999b28cd46c39473fa152c6fc3f2374061c53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Accumulation</topic><topic>Animals</topic><topic>Atrium</topic><topic>Biology and Life Sciences</topic><topic>Biotechnology</topic><topic>Bone marrow</topic><topic>Dilution</topic><topic>Disease Models, Animal</topic><topic>Fluorescence</topic><topic>Heart</topic><topic>Heart attack</topic><topic>Heart 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Ingo</au><au>Frati, Giacomo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Macroscopic fluorescence imaging: a novel technique to monitor retention and distribution of injected microspheres in an experimental model of ischemic heart failure</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-08-04</date><risdate>2014</risdate><volume>9</volume><issue>8</issue><spage>e101775</spage><epage>e101775</epage><pages>e101775-e101775</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The limited effectiveness of cardiac cell therapy has generated concern regarding its clinical relevance. Experimental studies show that cell retention and engraftment are low after injection into ischemic myocardium, which may restrict therapy effectiveness significantly. Surgical aspects and mechanical loss are suspected to be the main culprits behind this phenomenon. As current techniques of monitoring intramyocardial injections are complex and time-consuming, the aim of the study was to develop a fast and simple model to study cardiac retention and distribution following intramyocardial injections. For this purpose, our main hypothesis was that macroscopic fluorescence imaging could adequately serve as a detection method for intramyocardial injections.
A total of 20 mice underwent ligation of the left anterior descending artery (LAD) for myocardial infarction. Fluorescent microspheres with cellular dimensions were used as cell surrogates. Particles (5 × 10(5)) were injected into the infarcted area of explanted resting hearts (Ex vivo myocardial injetions EVMI, n = 10) and in vivo into beating hearts (In vivo myocardial injections IVMI, n = 10). Microsphere quantification was performed by fluorescence imaging of explanted organs. Measurements were repeated after a reduction to homogenate dilutions. Cardiac microsphere retention was 2.78 × 10(5) ± 0.31 × 10(5) in the EVMI group. In the IVMI group, cardiac retention of microspheres was significantly lower (0.74 × 10(5) ± 0.18 × 10(5); p<0.05). Direct fluorescence imaging revealed venous drainage through the coronary sinus, resulting in a microsphere accumulation in the left (0.90 × 10(5) ± 0.20 × 10(5)) and the right (1.07 × 10(5) ± 0.17 × 10(5)) lung. Processing to homogenates involved further particle loss (p<0.05) in both groups.
We developed a fast and simple direct fluorescence imaging method for biodistribution analysis which enabled the quantification of fluorescent microspheres after intramyocardial delivery using macroscopic fluorescence imaging. This new technique showed massive early particle loss and venous drainage into the right atrium leading to substantial accumulation of graft particles in both lungs.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25089764</pmid><doi>10.1371/journal.pone.0101775</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-08, Vol.9 (8), p.e101775-e101775 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1551148607 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Accumulation Animals Atrium Biology and Life Sciences Biotechnology Bone marrow Dilution Disease Models, Animal Fluorescence Heart Heart attack Heart attacks Heart diseases Heart failure Heart Failure - complications Heart Failure - diagnosis Heart surgery Imaging Injections Ischemia Laboratory animals Lungs Medical imaging Medical research Medical schools Medicine and Health Sciences Methods Mice, Inbred BALB C Microspheres Molecular Imaging - methods Myocardial infarction Myocardial Ischemia - complications Myocardial Ischemia - diagnosis Myocardium NMR Nuclear magnetic resonance Organs Reference Standards Reproducibility of Results Research and Analysis Methods Retention Stem cells Studies Surgery Therapy Vascular surgery |
| title | Macroscopic fluorescence imaging: a novel technique to monitor retention and distribution of injected microspheres in an experimental model of ischemic heart failure |
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