Vascular Endoluminal Delivery of Mesenchymal Stem Cells Using Acoustic Radiation Force
Restoration of functional endothelium is a requirement for preventing late stent thrombosis. We propose a novel method for targeted delivery of stem cells to a site of arterial injury using ultrasound-generated acoustic radiation force. Mesenchymal stem cells (MSCs) were surface-coated electrostatic...
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| Veröffentlicht in: | Tissue engineering. Part A 2011-05, Vol.17 (9-10), p.1457-1464 |
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| creator | Toma, Catalin Fisher, Andrew Wang, Jianjun Chen, Xucai Grata, Michelle Leeman, Jonathan Winston, Brion Kaya, Mehmet Fu, Huili Lavery, Linda Fischer, David Wagner, William R. Villanueva, Flordeliza S. |
| description | Restoration of functional endothelium is a requirement for preventing late stent thrombosis. We propose a novel method for targeted delivery of stem cells to a site of arterial injury using ultrasound-generated acoustic radiation force. Mesenchymal stem cells (MSCs) were surface-coated electrostatically with cationic gas-filled lipid microbubbles (mb-MSC). mb-MSC was characterized microscopically and by flow cytometry. The effect of ultrasound (5 MHz) on directing mb-MSC movement toward the vessel wall under physiologic flow conditions was tested
in vitro
in a vessel phantom.
In vivo
testing of acoustic radiation force-mediated delivery of mb-MSCs to balloon-injured aorta was performed in rabbits using intravascular ultrasound (1.7 MHz) during intra-aortic infusion of mb-MSCs. Application of ultrasound led to marginalization and adhesion of mb-MSCs to the vessel phantom wall, whereas no effect was observed on mb-MSCs in the absence of ultrasound. The effect was maximal when there were 7±1 microbubbles/cell (
n
=6). In rabbits (
n
=6), adherent MSCs were observed in the ultrasound-treated aortic segment 20 min after the injection (334±137 MSCs/cm
2
), whereas minimal adhesion was observed in control segments not exposed to ultrasound (2±1 MSCs/cm
2
,
p |
| doi_str_mv | 10.1089/ten.tea.2010.0539 |
| format | Article |
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in vitro
in a vessel phantom.
In vivo
testing of acoustic radiation force-mediated delivery of mb-MSCs to balloon-injured aorta was performed in rabbits using intravascular ultrasound (1.7 MHz) during intra-aortic infusion of mb-MSCs. Application of ultrasound led to marginalization and adhesion of mb-MSCs to the vessel phantom wall, whereas no effect was observed on mb-MSCs in the absence of ultrasound. The effect was maximal when there were 7±1 microbubbles/cell (
n
=6). In rabbits (
n
=6), adherent MSCs were observed in the ultrasound-treated aortic segment 20 min after the injection (334±137 MSCs/cm
2
), whereas minimal adhesion was observed in control segments not exposed to ultrasound (2±1 MSCs/cm
2
,
p
<0.05). At 24 h after mb-MSC injection and ultrasound treatment, the engrafted MSCs persisted and spread out on the luminal surface of the artery. The data demonstrate proof of principle that acoustic radiation force can target delivery of therapeutic cells to a specific endovascular treatment site. This approach may be used for endoluminal cellular paving and could provide a powerful tool for cell-based re-endothelialization of injured arterial segments.</description><identifier>ISSN: 1937-3341</identifier><identifier>EISSN: 1937-335X</identifier><identifier>DOI: 10.1089/ten.tea.2010.0539</identifier><identifier>PMID: 21247343</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Acoustic properties ; Acoustics ; Animals ; Aorta - injuries ; Aortic Diseases - therapy ; Biomedical engineering ; Blood clot ; Care and treatment ; Cell adhesion & migration ; Endothelium ; Graft Survival ; Mesenchymal Stem Cell Transplantation - methods ; Mesenchymal Stromal Cells ; Microbubbles ; Original ; Original Articles ; Physiological aspects ; Rabbits ; Radiation ; Rats ; Stem cells ; Thrombosis ; Tissue engineering ; Transplantation, Homologous ; Ultrasonics</subject><ispartof>Tissue engineering. Part A, 2011-05, Vol.17 (9-10), p.1457-1464</ispartof><rights>2011, Mary Ann Liebert, Inc.</rights><rights>COPYRIGHT 2011 Mary Ann Liebert, Inc.</rights><rights>(©) Copyright 2011, Mary Ann Liebert, Inc.</rights><rights>Copyright 2011, Mary Ann Liebert, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c620t-95faeb1408e9165e47c033fb2f340f4fdd2328135e85321ea2d78db8197a54d13</citedby><cites>FETCH-LOGICAL-c620t-95faeb1408e9165e47c033fb2f340f4fdd2328135e85321ea2d78db8197a54d13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21247343$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Toma, Catalin</creatorcontrib><creatorcontrib>Fisher, Andrew</creatorcontrib><creatorcontrib>Wang, Jianjun</creatorcontrib><creatorcontrib>Chen, Xucai</creatorcontrib><creatorcontrib>Grata, Michelle</creatorcontrib><creatorcontrib>Leeman, Jonathan</creatorcontrib><creatorcontrib>Winston, Brion</creatorcontrib><creatorcontrib>Kaya, Mehmet</creatorcontrib><creatorcontrib>Fu, Huili</creatorcontrib><creatorcontrib>Lavery, Linda</creatorcontrib><creatorcontrib>Fischer, David</creatorcontrib><creatorcontrib>Wagner, William R.</creatorcontrib><creatorcontrib>Villanueva, Flordeliza S.</creatorcontrib><title>Vascular Endoluminal Delivery of Mesenchymal Stem Cells Using Acoustic Radiation Force</title><title>Tissue engineering. Part A</title><addtitle>Tissue Eng Part A</addtitle><description>Restoration of functional endothelium is a requirement for preventing late stent thrombosis. We propose a novel method for targeted delivery of stem cells to a site of arterial injury using ultrasound-generated acoustic radiation force. Mesenchymal stem cells (MSCs) were surface-coated electrostatically with cationic gas-filled lipid microbubbles (mb-MSC). mb-MSC was characterized microscopically and by flow cytometry. The effect of ultrasound (5 MHz) on directing mb-MSC movement toward the vessel wall under physiologic flow conditions was tested
in vitro
in a vessel phantom.
In vivo
testing of acoustic radiation force-mediated delivery of mb-MSCs to balloon-injured aorta was performed in rabbits using intravascular ultrasound (1.7 MHz) during intra-aortic infusion of mb-MSCs. Application of ultrasound led to marginalization and adhesion of mb-MSCs to the vessel phantom wall, whereas no effect was observed on mb-MSCs in the absence of ultrasound. The effect was maximal when there were 7±1 microbubbles/cell (
n
=6). In rabbits (
n
=6), adherent MSCs were observed in the ultrasound-treated aortic segment 20 min after the injection (334±137 MSCs/cm
2
), whereas minimal adhesion was observed in control segments not exposed to ultrasound (2±1 MSCs/cm
2
,
p
<0.05). At 24 h after mb-MSC injection and ultrasound treatment, the engrafted MSCs persisted and spread out on the luminal surface of the artery. The data demonstrate proof of principle that acoustic radiation force can target delivery of therapeutic cells to a specific endovascular treatment site. This approach may be used for endoluminal cellular paving and could provide a powerful tool for cell-based re-endothelialization of injured arterial segments.</description><subject>Acoustic properties</subject><subject>Acoustics</subject><subject>Animals</subject><subject>Aorta - injuries</subject><subject>Aortic Diseases - therapy</subject><subject>Biomedical engineering</subject><subject>Blood clot</subject><subject>Care and treatment</subject><subject>Cell adhesion & migration</subject><subject>Endothelium</subject><subject>Graft Survival</subject><subject>Mesenchymal Stem Cell Transplantation - methods</subject><subject>Mesenchymal Stromal Cells</subject><subject>Microbubbles</subject><subject>Original</subject><subject>Original Articles</subject><subject>Physiological aspects</subject><subject>Rabbits</subject><subject>Radiation</subject><subject>Rats</subject><subject>Stem cells</subject><subject>Thrombosis</subject><subject>Tissue engineering</subject><subject>Transplantation, Homologous</subject><subject>Ultrasonics</subject><issn>1937-3341</issn><issn>1937-335X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNUl1rFDEUHUSxtfUH-CKDPvi0az4mk8yLsKytCi1CtcW3kElutimZpE1mCvvvzbB1scUHCSHh5JxzuTenqt5gtMRIdB9HCMsR1JKggiBGu2fVIe4oX1DKfj3f3xt8UL3K-QahFrWcv6wOCCYNpw09rK6uVNaTV6k-CSb6aXBB-fozeHcPaVtHW59DhqCvt0PBf4ww1GvwPteX2YVNvdJxyqPT9YUyTo0uhvo0Jg3H1QurfIbXD-dRdXl68nP9dXH2_cu39epsoVuCxkXHrIIeN0hAh1sGDdeIUtsTSxtkG2sMoURgykAwSjAoYrgwvcAdV6wxmB5Vn3a-t1M_gNEQxqS8vE1uUGkro3Ly8Utw13IT7yVFfK5YDD48GKR4N0Ee5eCyLh2qAKU1KdqOCY45Kcx3T5g3cUplWjOJCCbKlxTS-x1pozxIF2wsVfVsKVeEtZhjhuaiy3-wyjIwOB0DWFfwRwK8E-gUc05g9x1iJOcoyBKFspWcoyDnKBTN279Hs1f8-ftC4DvCDKsQvIMe0vgf1r8B1PjCoQ</recordid><startdate>20110501</startdate><enddate>20110501</enddate><creator>Toma, Catalin</creator><creator>Fisher, Andrew</creator><creator>Wang, Jianjun</creator><creator>Chen, Xucai</creator><creator>Grata, Michelle</creator><creator>Leeman, Jonathan</creator><creator>Winston, Brion</creator><creator>Kaya, Mehmet</creator><creator>Fu, Huili</creator><creator>Lavery, Linda</creator><creator>Fischer, David</creator><creator>Wagner, William R.</creator><creator>Villanueva, Flordeliza S.</creator><general>Mary Ann Liebert, Inc</general><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>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20110501</creationdate><title>Vascular Endoluminal Delivery of Mesenchymal Stem Cells Using Acoustic Radiation Force</title><author>Toma, Catalin ; Fisher, Andrew ; Wang, Jianjun ; Chen, Xucai ; Grata, Michelle ; Leeman, Jonathan ; Winston, Brion ; Kaya, Mehmet ; Fu, Huili ; Lavery, Linda ; Fischer, David ; Wagner, William R. ; Villanueva, Flordeliza S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c620t-95faeb1408e9165e47c033fb2f340f4fdd2328135e85321ea2d78db8197a54d13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Acoustic properties</topic><topic>Acoustics</topic><topic>Animals</topic><topic>Aorta - injuries</topic><topic>Aortic Diseases - therapy</topic><topic>Biomedical engineering</topic><topic>Blood clot</topic><topic>Care and treatment</topic><topic>Cell adhesion & migration</topic><topic>Endothelium</topic><topic>Graft Survival</topic><topic>Mesenchymal Stem Cell Transplantation - methods</topic><topic>Mesenchymal Stromal Cells</topic><topic>Microbubbles</topic><topic>Original</topic><topic>Original Articles</topic><topic>Physiological aspects</topic><topic>Rabbits</topic><topic>Radiation</topic><topic>Rats</topic><topic>Stem cells</topic><topic>Thrombosis</topic><topic>Tissue engineering</topic><topic>Transplantation, Homologous</topic><topic>Ultrasonics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Toma, Catalin</creatorcontrib><creatorcontrib>Fisher, Andrew</creatorcontrib><creatorcontrib>Wang, Jianjun</creatorcontrib><creatorcontrib>Chen, Xucai</creatorcontrib><creatorcontrib>Grata, Michelle</creatorcontrib><creatorcontrib>Leeman, Jonathan</creatorcontrib><creatorcontrib>Winston, Brion</creatorcontrib><creatorcontrib>Kaya, Mehmet</creatorcontrib><creatorcontrib>Fu, Huili</creatorcontrib><creatorcontrib>Lavery, Linda</creatorcontrib><creatorcontrib>Fischer, David</creatorcontrib><creatorcontrib>Wagner, William R.</creatorcontrib><creatorcontrib>Villanueva, Flordeliza S.</creatorcontrib><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>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science 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 Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science 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>ProQuest Central Basic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Tissue engineering. Part A</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Toma, Catalin</au><au>Fisher, Andrew</au><au>Wang, Jianjun</au><au>Chen, Xucai</au><au>Grata, Michelle</au><au>Leeman, Jonathan</au><au>Winston, Brion</au><au>Kaya, Mehmet</au><au>Fu, Huili</au><au>Lavery, Linda</au><au>Fischer, David</au><au>Wagner, William R.</au><au>Villanueva, Flordeliza S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vascular Endoluminal Delivery of Mesenchymal Stem Cells Using Acoustic Radiation Force</atitle><jtitle>Tissue engineering. Part A</jtitle><addtitle>Tissue Eng Part A</addtitle><date>2011-05-01</date><risdate>2011</risdate><volume>17</volume><issue>9-10</issue><spage>1457</spage><epage>1464</epage><pages>1457-1464</pages><issn>1937-3341</issn><eissn>1937-335X</eissn><abstract>Restoration of functional endothelium is a requirement for preventing late stent thrombosis. We propose a novel method for targeted delivery of stem cells to a site of arterial injury using ultrasound-generated acoustic radiation force. Mesenchymal stem cells (MSCs) were surface-coated electrostatically with cationic gas-filled lipid microbubbles (mb-MSC). mb-MSC was characterized microscopically and by flow cytometry. The effect of ultrasound (5 MHz) on directing mb-MSC movement toward the vessel wall under physiologic flow conditions was tested
in vitro
in a vessel phantom.
In vivo
testing of acoustic radiation force-mediated delivery of mb-MSCs to balloon-injured aorta was performed in rabbits using intravascular ultrasound (1.7 MHz) during intra-aortic infusion of mb-MSCs. Application of ultrasound led to marginalization and adhesion of mb-MSCs to the vessel phantom wall, whereas no effect was observed on mb-MSCs in the absence of ultrasound. The effect was maximal when there were 7±1 microbubbles/cell (
n
=6). In rabbits (
n
=6), adherent MSCs were observed in the ultrasound-treated aortic segment 20 min after the injection (334±137 MSCs/cm
2
), whereas minimal adhesion was observed in control segments not exposed to ultrasound (2±1 MSCs/cm
2
,
p
<0.05). At 24 h after mb-MSC injection and ultrasound treatment, the engrafted MSCs persisted and spread out on the luminal surface of the artery. The data demonstrate proof of principle that acoustic radiation force can target delivery of therapeutic cells to a specific endovascular treatment site. This approach may be used for endoluminal cellular paving and could provide a powerful tool for cell-based re-endothelialization of injured arterial segments.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>21247343</pmid><doi>10.1089/ten.tea.2010.0539</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1937-3341 |
| ispartof | Tissue engineering. Part A, 2011-05, Vol.17 (9-10), p.1457-1464 |
| issn | 1937-3341 1937-335X |
| language | eng |
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| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Acoustic properties Acoustics Animals Aorta - injuries Aortic Diseases - therapy Biomedical engineering Blood clot Care and treatment Cell adhesion & migration Endothelium Graft Survival Mesenchymal Stem Cell Transplantation - methods Mesenchymal Stromal Cells Microbubbles Original Original Articles Physiological aspects Rabbits Radiation Rats Stem cells Thrombosis Tissue engineering Transplantation, Homologous Ultrasonics |
| title | Vascular Endoluminal Delivery of Mesenchymal Stem Cells Using Acoustic Radiation Force |
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