Immune-modulatory alginate protects mesenchymal stem cells for sustained delivery of reparative factors to ischemic myocardium
Paracrine factors secreted by mesenchymal stem cells (MSCs) have been previously shown to improve cardiac function following acute myocardial infarction (MI). However, cell therapy activates the innate immune response, leading to the rapid elimination of transplanted cells and only short-term therap...
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| Veröffentlicht in: | Biomaterials science 2020-09, Vol.8 (18), p.561-57 |
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| creator | Ghanta, Ravi K Aghlara-Fotovat, Samira Pugazenthi, Aarthi Ryan, Christopher T Singh, Vivek P Mathison, Megumi Jarvis, Maria I Mukherjee, Sudip Hernandez, Andrea Veiseh, Omid |
| description | Paracrine factors secreted by mesenchymal stem cells (MSCs) have been previously shown to improve cardiac function following acute myocardial infarction (MI). However, cell therapy activates the innate immune response, leading to the rapid elimination of transplanted cells and only short-term therapeutic delivery. Herein, we describe a new strategy to deliver sustained paracrine-mediated MSC therapy to ischemic myocardium. Using an immune evasive, small molecule modified alginate, we encapsulated rat MSC cells in a core-shell hydrogel capsule and implanted them in the pericardial sac of post-MI rats. Encapsulated cells allowed diffusion of reparative paracrine factors at levels similar to non-encapsulated cells
in vitro
. Encapsulation enabled sustained cell survival with localization over the heart for 2 weeks. The effect of the experimental group on ventricular function and fibrosis was compared with blank (cell free) capsules and unencapsulated MSCs injected into infarcted myocardium. MSC capsules improved post-MI ventricular function ∼2.5× greater than MSC injection. After 4 weeks, post-MI fibrosis was reduced ∼2/3 with MSC capsules, but unchanged with MSC injection. MSC encapsulation with alginate core-shell capsules sustains cell survival and potentiates efficacy of therapy.
Immune modulatory alginate encapsulation platform can be used in the pericardial space to provide enhanced therapeutic efficacy to the heart. |
| doi_str_mv | 10.1039/d0bm00855a |
| format | Article |
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in vitro
. Encapsulation enabled sustained cell survival with localization over the heart for 2 weeks. The effect of the experimental group on ventricular function and fibrosis was compared with blank (cell free) capsules and unencapsulated MSCs injected into infarcted myocardium. MSC capsules improved post-MI ventricular function ∼2.5× greater than MSC injection. After 4 weeks, post-MI fibrosis was reduced ∼2/3 with MSC capsules, but unchanged with MSC injection. MSC encapsulation with alginate core-shell capsules sustains cell survival and potentiates efficacy of therapy.
Immune modulatory alginate encapsulation platform can be used in the pericardial space to provide enhanced therapeutic efficacy to the heart.</description><identifier>ISSN: 2047-4830</identifier><identifier>EISSN: 2047-4849</identifier><identifier>DOI: 10.1039/d0bm00855a</identifier><identifier>PMID: 32797143</identifier><language>eng</language><publisher>CAMBRIDGE: Royal Soc Chemistry</publisher><subject>Alginates ; Animals ; Encapsulation ; Fibrosis ; Hydrogels ; Immune system ; Materials Science ; Materials Science, Biomaterials ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells ; Myocardial infarction ; Myocardial Infarction - therapy ; Myocardium ; Rats ; Science & Technology ; Stem cells ; Survival ; Technology ; Therapy</subject><ispartof>Biomaterials science, 2020-09, Vol.8 (18), p.561-57</ispartof><rights>Copyright Royal Society of Chemistry 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>25</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000569877500009</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c495t-6eb80655455cce377a7b985b1dbf8b8c49c7344362790611aed6a8a2c013c7073</citedby><cites>FETCH-LOGICAL-c495t-6eb80655455cce377a7b985b1dbf8b8c49c7344362790611aed6a8a2c013c7073</cites><orcidid>0000-0003-1153-8079 ; 0000-0001-9301-3780</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,782,786,887,27933,27934,28257</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32797143$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ghanta, Ravi K</creatorcontrib><creatorcontrib>Aghlara-Fotovat, Samira</creatorcontrib><creatorcontrib>Pugazenthi, Aarthi</creatorcontrib><creatorcontrib>Ryan, Christopher T</creatorcontrib><creatorcontrib>Singh, Vivek P</creatorcontrib><creatorcontrib>Mathison, Megumi</creatorcontrib><creatorcontrib>Jarvis, Maria I</creatorcontrib><creatorcontrib>Mukherjee, Sudip</creatorcontrib><creatorcontrib>Hernandez, Andrea</creatorcontrib><creatorcontrib>Veiseh, Omid</creatorcontrib><title>Immune-modulatory alginate protects mesenchymal stem cells for sustained delivery of reparative factors to ischemic myocardium</title><title>Biomaterials science</title><addtitle>BIOMATER SCI-UK</addtitle><addtitle>Biomater Sci</addtitle><description>Paracrine factors secreted by mesenchymal stem cells (MSCs) have been previously shown to improve cardiac function following acute myocardial infarction (MI). However, cell therapy activates the innate immune response, leading to the rapid elimination of transplanted cells and only short-term therapeutic delivery. Herein, we describe a new strategy to deliver sustained paracrine-mediated MSC therapy to ischemic myocardium. Using an immune evasive, small molecule modified alginate, we encapsulated rat MSC cells in a core-shell hydrogel capsule and implanted them in the pericardial sac of post-MI rats. Encapsulated cells allowed diffusion of reparative paracrine factors at levels similar to non-encapsulated cells
in vitro
. Encapsulation enabled sustained cell survival with localization over the heart for 2 weeks. The effect of the experimental group on ventricular function and fibrosis was compared with blank (cell free) capsules and unencapsulated MSCs injected into infarcted myocardium. MSC capsules improved post-MI ventricular function ∼2.5× greater than MSC injection. After 4 weeks, post-MI fibrosis was reduced ∼2/3 with MSC capsules, but unchanged with MSC injection. MSC encapsulation with alginate core-shell capsules sustains cell survival and potentiates efficacy of therapy.
Immune modulatory alginate encapsulation platform can be used in the pericardial space to provide enhanced therapeutic efficacy to the heart.</description><subject>Alginates</subject><subject>Animals</subject><subject>Encapsulation</subject><subject>Fibrosis</subject><subject>Hydrogels</subject><subject>Immune system</subject><subject>Materials Science</subject><subject>Materials Science, Biomaterials</subject><subject>Mesenchymal Stem Cell Transplantation</subject><subject>Mesenchymal Stem Cells</subject><subject>Myocardial infarction</subject><subject>Myocardial Infarction - therapy</subject><subject>Myocardium</subject><subject>Rats</subject><subject>Science & Technology</subject><subject>Stem cells</subject><subject>Survival</subject><subject>Technology</subject><subject>Therapy</subject><issn>2047-4830</issn><issn>2047-4849</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AOWDO</sourceid><sourceid>EIF</sourceid><recordid>eNqNkktv1TAQhSMEolXphj3IiA0CBZzYjp0NUrm8KhWxgbXlOJNeV3Gc2k7R3fDbmfaW8FggvLGt-eZ4xmeK4mFFX1aUta962nlKlRDmTnFYUy5Lrnh7dz0zelAcp3RBcUnZ0qa6XxywWray4uyw-H7q_TJB6UO_jCaHuCNmPHeTyUDmGDLYnIiHBJPd7rwZScrgiYVxTGQIkaQlZeMm6EkPo7sCzA8DiTCbaDLeyWAsqiaSA3HJbsE7S_wuWBN7t_gHxb3BjAmOb_ej4uv7d182H8uzzx9ONydnpeWtyGUDnaKNEFwIa4FJaWTXKtFVfTeoTiFkJeOcNfVNh5WBvjHK1JZWzEoq2VHxeq87L52H3sKUoxn1HJ03caeDcfrPyOS2-jxcaclbLmqBAs9uBWK4XCBl7bEd_AYzQViSrjm-r6pGckSf_oVehCVO2B5SvG4oZ7RG6vmesjGkFGFYi6movnZWv6VvPt04e4Lw49_LX9GfPiLwYg98gy4MyTr0C1YMrRdNq6QU11PQIq3-n964jE6GaROWKWPqo31qTHbN-DWDGH_yr7ie-4H9ACoj10A</recordid><startdate>20200915</startdate><enddate>20200915</enddate><creator>Ghanta, Ravi K</creator><creator>Aghlara-Fotovat, Samira</creator><creator>Pugazenthi, Aarthi</creator><creator>Ryan, Christopher T</creator><creator>Singh, Vivek P</creator><creator>Mathison, Megumi</creator><creator>Jarvis, Maria I</creator><creator>Mukherjee, Sudip</creator><creator>Hernandez, Andrea</creator><creator>Veiseh, Omid</creator><general>Royal Soc Chemistry</general><general>Royal Society of Chemistry</general><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</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>7SR</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1153-8079</orcidid><orcidid>https://orcid.org/0000-0001-9301-3780</orcidid></search><sort><creationdate>20200915</creationdate><title>Immune-modulatory alginate protects mesenchymal stem cells for sustained delivery of reparative factors to ischemic myocardium</title><author>Ghanta, Ravi K ; Aghlara-Fotovat, Samira ; Pugazenthi, Aarthi ; Ryan, Christopher T ; Singh, Vivek P ; Mathison, Megumi ; Jarvis, Maria I ; Mukherjee, Sudip ; Hernandez, Andrea ; Veiseh, Omid</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c495t-6eb80655455cce377a7b985b1dbf8b8c49c7344362790611aed6a8a2c013c7073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Alginates</topic><topic>Animals</topic><topic>Encapsulation</topic><topic>Fibrosis</topic><topic>Hydrogels</topic><topic>Immune system</topic><topic>Materials Science</topic><topic>Materials Science, Biomaterials</topic><topic>Mesenchymal Stem Cell Transplantation</topic><topic>Mesenchymal Stem Cells</topic><topic>Myocardial infarction</topic><topic>Myocardial Infarction - therapy</topic><topic>Myocardium</topic><topic>Rats</topic><topic>Science & Technology</topic><topic>Stem cells</topic><topic>Survival</topic><topic>Technology</topic><topic>Therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ghanta, Ravi K</creatorcontrib><creatorcontrib>Aghlara-Fotovat, Samira</creatorcontrib><creatorcontrib>Pugazenthi, Aarthi</creatorcontrib><creatorcontrib>Ryan, Christopher T</creatorcontrib><creatorcontrib>Singh, Vivek P</creatorcontrib><creatorcontrib>Mathison, Megumi</creatorcontrib><creatorcontrib>Jarvis, Maria I</creatorcontrib><creatorcontrib>Mukherjee, Sudip</creatorcontrib><creatorcontrib>Hernandez, Andrea</creatorcontrib><creatorcontrib>Veiseh, Omid</creatorcontrib><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biomaterials science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ghanta, Ravi K</au><au>Aghlara-Fotovat, Samira</au><au>Pugazenthi, Aarthi</au><au>Ryan, Christopher T</au><au>Singh, Vivek P</au><au>Mathison, Megumi</au><au>Jarvis, Maria I</au><au>Mukherjee, Sudip</au><au>Hernandez, Andrea</au><au>Veiseh, Omid</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immune-modulatory alginate protects mesenchymal stem cells for sustained delivery of reparative factors to ischemic myocardium</atitle><jtitle>Biomaterials science</jtitle><stitle>BIOMATER SCI-UK</stitle><addtitle>Biomater Sci</addtitle><date>2020-09-15</date><risdate>2020</risdate><volume>8</volume><issue>18</issue><spage>561</spage><epage>57</epage><pages>561-57</pages><issn>2047-4830</issn><eissn>2047-4849</eissn><abstract>Paracrine factors secreted by mesenchymal stem cells (MSCs) have been previously shown to improve cardiac function following acute myocardial infarction (MI). However, cell therapy activates the innate immune response, leading to the rapid elimination of transplanted cells and only short-term therapeutic delivery. Herein, we describe a new strategy to deliver sustained paracrine-mediated MSC therapy to ischemic myocardium. Using an immune evasive, small molecule modified alginate, we encapsulated rat MSC cells in a core-shell hydrogel capsule and implanted them in the pericardial sac of post-MI rats. Encapsulated cells allowed diffusion of reparative paracrine factors at levels similar to non-encapsulated cells
in vitro
. Encapsulation enabled sustained cell survival with localization over the heart for 2 weeks. The effect of the experimental group on ventricular function and fibrosis was compared with blank (cell free) capsules and unencapsulated MSCs injected into infarcted myocardium. MSC capsules improved post-MI ventricular function ∼2.5× greater than MSC injection. After 4 weeks, post-MI fibrosis was reduced ∼2/3 with MSC capsules, but unchanged with MSC injection. MSC encapsulation with alginate core-shell capsules sustains cell survival and potentiates efficacy of therapy.
Immune modulatory alginate encapsulation platform can be used in the pericardial space to provide enhanced therapeutic efficacy to the heart.</abstract><cop>CAMBRIDGE</cop><pub>Royal Soc Chemistry</pub><pmid>32797143</pmid><doi>10.1039/d0bm00855a</doi><orcidid>https://orcid.org/0000-0003-1153-8079</orcidid><orcidid>https://orcid.org/0000-0001-9301-3780</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Alginates Animals Encapsulation Fibrosis Hydrogels Immune system Materials Science Materials Science, Biomaterials Mesenchymal Stem Cell Transplantation Mesenchymal Stem Cells Myocardial infarction Myocardial Infarction - therapy Myocardium Rats Science & Technology Stem cells Survival Technology Therapy |
| title | Immune-modulatory alginate protects mesenchymal stem cells for sustained delivery of reparative factors to ischemic myocardium |
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