Treatment of Abdominal Aortic Aneurysm Utilizing Adipose-Derived Mesenchymal Stem Cells in a Porcine Model
The current treatment paradigm of abdominal aortic aneurysms (AAA) focuses on observing patients until their disease reaches certain thresholds for intervention, with no preceding treatment available. There is an opportunity to develop novel therapies to prevent further aneurysmal growth and decreas...
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| Veröffentlicht in: | The Journal of surgical research 2022-10, Vol.278, p.247-256 |
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| creator | Zilberman, Brian Kooragayala, Keshav Lou, Johanna Ghobrial, Gaby De Leo, Nicholas Emery, Robert Ostrovsky, Olga Zhang, Ping Platoff, Rebecca Zhu, Clara Hunter, Krystal Delong, Drew Hong, Young Brown, Spencer A. Carpenter, Jeffrey P. |
| description | The current treatment paradigm of abdominal aortic aneurysms (AAA) focuses on observing patients until their disease reaches certain thresholds for intervention, with no preceding treatment available. There is an opportunity to develop novel therapies to prevent further aneurysmal growth and decrease the risk of a highly morbid rupture. We used a porcine model of aortic dilation to assess the ability of human adipose-derived mesenchymal stem cells (MSCs) to attenuate aortic dilation.
Twelve Yorkshire pigs received periadventitial injections (collagenase and elastase) into a 4-cm segment of infrarenal aorta. Animals were treated with either 1 × 106 MSCs placed onto Gelfoam or treated with media as a control. Aortic diameters were measured at the time of surgery and monitored at postoperative day (POD) 7 and 14 with ultrasound. Animals were sacrificed on POD 21. Aortic tissue was harvested for histopathological analyses and immunohistochemistry. Groups were compared with paired t-tests or Mann–Whitney U-tests.
All animals survived until POD 21. The mean aortic diameter was reduced in the aortic dilation + MSC treatment group compared to aortic dilation control animals (1.10 ± 0.126 versus 1.48 cm ± 0.151, P |
| doi_str_mv | 10.1016/j.jss.2022.04.064 |
| format | Article |
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Twelve Yorkshire pigs received periadventitial injections (collagenase and elastase) into a 4-cm segment of infrarenal aorta. Animals were treated with either 1 × 106 MSCs placed onto Gelfoam or treated with media as a control. Aortic diameters were measured at the time of surgery and monitored at postoperative day (POD) 7 and 14 with ultrasound. Animals were sacrificed on POD 21. Aortic tissue was harvested for histopathological analyses and immunohistochemistry. Groups were compared with paired t-tests or Mann–Whitney U-tests.
All animals survived until POD 21. The mean aortic diameter was reduced in the aortic dilation + MSC treatment group compared to aortic dilation control animals (1.10 ± 0.126 versus 1.48 cm ± 0.151, P < 0.001). Aortic media thickness was reduced in the aortic dilation group compared to the aortic dilation + MSC group (609.14 IQR 445.21-692.93 μm versus 643.55 IQR 560.91-733.88 μm, P = 0.0048). There was a significant decrease in the content of collagen and alpha-smooth muscle actin and elastin perturbation in the aortic dilation group as compared to the aortic dilation + MSC group. Immunohistochemistry demonstrated an increased level of vascular endothelial growth factor, tissue inhibitor of matrix metalloproteinase 1, and tissue inhibitor of matrix metalloproteinase 3 expression in the aorta of aortic dilation + MSC animals.
Stem cell therapy suppressed the aortic dilation in a porcine model. Animals from the aortic dilation group showed more diseased gross features, histologic changes, and biochemical properties of the aorta compared to that of the aortic dilation + MSC treated animals. This novel finding should prompt further investigation into translatable drug and cell therapies for aneurysmal disease.</description><identifier>ISSN: 0022-4804</identifier><identifier>EISSN: 1095-8673</identifier><identifier>DOI: 10.1016/j.jss.2022.04.064</identifier><identifier>PMID: 35636200</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Aortic aneurysm ; Stem cell therapy</subject><ispartof>The Journal of surgical research, 2022-10, Vol.278, p.247-256</ispartof><rights>2022 Elsevier Inc.</rights><rights>Copyright © 2022 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-3e30eae706dad4def4889b8efa9fff7035e53ae85a94ee8f8900c23e225fac613</citedby><cites>FETCH-LOGICAL-c353t-3e30eae706dad4def4889b8efa9fff7035e53ae85a94ee8f8900c23e225fac613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jss.2022.04.064$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35636200$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zilberman, Brian</creatorcontrib><creatorcontrib>Kooragayala, Keshav</creatorcontrib><creatorcontrib>Lou, Johanna</creatorcontrib><creatorcontrib>Ghobrial, Gaby</creatorcontrib><creatorcontrib>De Leo, Nicholas</creatorcontrib><creatorcontrib>Emery, Robert</creatorcontrib><creatorcontrib>Ostrovsky, Olga</creatorcontrib><creatorcontrib>Zhang, Ping</creatorcontrib><creatorcontrib>Platoff, Rebecca</creatorcontrib><creatorcontrib>Zhu, Clara</creatorcontrib><creatorcontrib>Hunter, Krystal</creatorcontrib><creatorcontrib>Delong, Drew</creatorcontrib><creatorcontrib>Hong, Young</creatorcontrib><creatorcontrib>Brown, Spencer A.</creatorcontrib><creatorcontrib>Carpenter, Jeffrey P.</creatorcontrib><title>Treatment of Abdominal Aortic Aneurysm Utilizing Adipose-Derived Mesenchymal Stem Cells in a Porcine Model</title><title>The Journal of surgical research</title><addtitle>J Surg Res</addtitle><description>The current treatment paradigm of abdominal aortic aneurysms (AAA) focuses on observing patients until their disease reaches certain thresholds for intervention, with no preceding treatment available. There is an opportunity to develop novel therapies to prevent further aneurysmal growth and decrease the risk of a highly morbid rupture. We used a porcine model of aortic dilation to assess the ability of human adipose-derived mesenchymal stem cells (MSCs) to attenuate aortic dilation.
Twelve Yorkshire pigs received periadventitial injections (collagenase and elastase) into a 4-cm segment of infrarenal aorta. Animals were treated with either 1 × 106 MSCs placed onto Gelfoam or treated with media as a control. Aortic diameters were measured at the time of surgery and monitored at postoperative day (POD) 7 and 14 with ultrasound. Animals were sacrificed on POD 21. Aortic tissue was harvested for histopathological analyses and immunohistochemistry. Groups were compared with paired t-tests or Mann–Whitney U-tests.
All animals survived until POD 21. The mean aortic diameter was reduced in the aortic dilation + MSC treatment group compared to aortic dilation control animals (1.10 ± 0.126 versus 1.48 cm ± 0.151, P < 0.001). Aortic media thickness was reduced in the aortic dilation group compared to the aortic dilation + MSC group (609.14 IQR 445.21-692.93 μm versus 643.55 IQR 560.91-733.88 μm, P = 0.0048). There was a significant decrease in the content of collagen and alpha-smooth muscle actin and elastin perturbation in the aortic dilation group as compared to the aortic dilation + MSC group. Immunohistochemistry demonstrated an increased level of vascular endothelial growth factor, tissue inhibitor of matrix metalloproteinase 1, and tissue inhibitor of matrix metalloproteinase 3 expression in the aorta of aortic dilation + MSC animals.
Stem cell therapy suppressed the aortic dilation in a porcine model. Animals from the aortic dilation group showed more diseased gross features, histologic changes, and biochemical properties of the aorta compared to that of the aortic dilation + MSC treated animals. This novel finding should prompt further investigation into translatable drug and cell therapies for aneurysmal disease.</description><subject>Aortic aneurysm</subject><subject>Stem cell therapy</subject><issn>0022-4804</issn><issn>1095-8673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp9kE1P3DAQhi1UBFvaH8Cl8rGXpBM7cWJxipZ-SSAqAWfLa4-poyRe7CzS9tdjtMCxJ2vk53018xByXkFZQSW-DeWQUsmAsRLqEkR9RFYVyKboRMs_kBXkn6LuoD4lH1MaIM-y5SfklDeCCwawIsNdRL1MOC80ONpvbJj8rEfah7h4Q_sZd3GfJnq_-NH_8_MD7a3fhoTFJUb_hJZeY8LZ_N1POXW74ETXOI6J-plq-idE42ek18Hi-IkcOz0m_Pz6npH7H9_v1r-Kq5ufv9f9VWF4w5eCIwfU2IKw2tYWXd11ctOh09I51wJvsOEau0bLGrFznQQwjCNjjdNGVPyMfD30bmN43GFa1OSTyUvpGcMuKSbaSkrJhMxodUBNDClFdGob_aTjXlWgXhSrQWXF6kWxglplxTnz5bV-t5nQvifenGbg4gBgPvLJY1TJ-KwIrY9oFmWD_0_9MwIPjZU</recordid><startdate>20221001</startdate><enddate>20221001</enddate><creator>Zilberman, Brian</creator><creator>Kooragayala, Keshav</creator><creator>Lou, Johanna</creator><creator>Ghobrial, Gaby</creator><creator>De Leo, Nicholas</creator><creator>Emery, Robert</creator><creator>Ostrovsky, Olga</creator><creator>Zhang, Ping</creator><creator>Platoff, Rebecca</creator><creator>Zhu, Clara</creator><creator>Hunter, Krystal</creator><creator>Delong, Drew</creator><creator>Hong, Young</creator><creator>Brown, Spencer A.</creator><creator>Carpenter, Jeffrey P.</creator><general>Elsevier Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20221001</creationdate><title>Treatment of Abdominal Aortic Aneurysm Utilizing Adipose-Derived Mesenchymal Stem Cells in a Porcine Model</title><author>Zilberman, Brian ; Kooragayala, Keshav ; Lou, Johanna ; Ghobrial, Gaby ; De Leo, Nicholas ; Emery, Robert ; Ostrovsky, Olga ; Zhang, Ping ; Platoff, Rebecca ; Zhu, Clara ; Hunter, Krystal ; Delong, Drew ; Hong, Young ; Brown, Spencer A. ; Carpenter, Jeffrey P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-3e30eae706dad4def4889b8efa9fff7035e53ae85a94ee8f8900c23e225fac613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Aortic aneurysm</topic><topic>Stem cell therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zilberman, Brian</creatorcontrib><creatorcontrib>Kooragayala, Keshav</creatorcontrib><creatorcontrib>Lou, Johanna</creatorcontrib><creatorcontrib>Ghobrial, Gaby</creatorcontrib><creatorcontrib>De Leo, Nicholas</creatorcontrib><creatorcontrib>Emery, Robert</creatorcontrib><creatorcontrib>Ostrovsky, Olga</creatorcontrib><creatorcontrib>Zhang, Ping</creatorcontrib><creatorcontrib>Platoff, Rebecca</creatorcontrib><creatorcontrib>Zhu, Clara</creatorcontrib><creatorcontrib>Hunter, Krystal</creatorcontrib><creatorcontrib>Delong, Drew</creatorcontrib><creatorcontrib>Hong, Young</creatorcontrib><creatorcontrib>Brown, Spencer A.</creatorcontrib><creatorcontrib>Carpenter, Jeffrey P.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of surgical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zilberman, Brian</au><au>Kooragayala, Keshav</au><au>Lou, Johanna</au><au>Ghobrial, Gaby</au><au>De Leo, Nicholas</au><au>Emery, Robert</au><au>Ostrovsky, Olga</au><au>Zhang, Ping</au><au>Platoff, Rebecca</au><au>Zhu, Clara</au><au>Hunter, Krystal</au><au>Delong, Drew</au><au>Hong, Young</au><au>Brown, Spencer A.</au><au>Carpenter, Jeffrey P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Treatment of Abdominal Aortic Aneurysm Utilizing Adipose-Derived Mesenchymal Stem Cells in a Porcine Model</atitle><jtitle>The Journal of surgical research</jtitle><addtitle>J Surg Res</addtitle><date>2022-10-01</date><risdate>2022</risdate><volume>278</volume><spage>247</spage><epage>256</epage><pages>247-256</pages><issn>0022-4804</issn><eissn>1095-8673</eissn><abstract>The current treatment paradigm of abdominal aortic aneurysms (AAA) focuses on observing patients until their disease reaches certain thresholds for intervention, with no preceding treatment available. There is an opportunity to develop novel therapies to prevent further aneurysmal growth and decrease the risk of a highly morbid rupture. We used a porcine model of aortic dilation to assess the ability of human adipose-derived mesenchymal stem cells (MSCs) to attenuate aortic dilation.
Twelve Yorkshire pigs received periadventitial injections (collagenase and elastase) into a 4-cm segment of infrarenal aorta. Animals were treated with either 1 × 106 MSCs placed onto Gelfoam or treated with media as a control. Aortic diameters were measured at the time of surgery and monitored at postoperative day (POD) 7 and 14 with ultrasound. Animals were sacrificed on POD 21. Aortic tissue was harvested for histopathological analyses and immunohistochemistry. Groups were compared with paired t-tests or Mann–Whitney U-tests.
All animals survived until POD 21. The mean aortic diameter was reduced in the aortic dilation + MSC treatment group compared to aortic dilation control animals (1.10 ± 0.126 versus 1.48 cm ± 0.151, P < 0.001). Aortic media thickness was reduced in the aortic dilation group compared to the aortic dilation + MSC group (609.14 IQR 445.21-692.93 μm versus 643.55 IQR 560.91-733.88 μm, P = 0.0048). There was a significant decrease in the content of collagen and alpha-smooth muscle actin and elastin perturbation in the aortic dilation group as compared to the aortic dilation + MSC group. Immunohistochemistry demonstrated an increased level of vascular endothelial growth factor, tissue inhibitor of matrix metalloproteinase 1, and tissue inhibitor of matrix metalloproteinase 3 expression in the aorta of aortic dilation + MSC animals.
Stem cell therapy suppressed the aortic dilation in a porcine model. Animals from the aortic dilation group showed more diseased gross features, histologic changes, and biochemical properties of the aorta compared to that of the aortic dilation + MSC treated animals. This novel finding should prompt further investigation into translatable drug and cell therapies for aneurysmal disease.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>35636200</pmid><doi>10.1016/j.jss.2022.04.064</doi><tpages>10</tpages></addata></record> |
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| subjects | Aortic aneurysm Stem cell therapy |
| title | Treatment of Abdominal Aortic Aneurysm Utilizing Adipose-Derived Mesenchymal Stem Cells in a Porcine Model |
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