{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:55:07Z","timestamp":1787018107619,"version":"build-2736575974"},"reference-count":88,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,5,7]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Cellular therapies have been investigated to improve blood flow and prevent amputation in peripheral artery disease with limited efficacy in clinical trials. Alginate\u2010encapsulated mesenchymal stromal cells (eMSCs) demonstrated improved retention and survival and promoted vascular generation in murine hind limb ischemia through their secretome, but large animal evaluation is necessary for human applicability. We sought to determine the efficacy of eMSCs for peripheral artery disease\u2013induced limb ischemia through assessment in our durable swine hind limb ischemia model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Autologous bone marrow eMSCs or empty alginate capsules were intramuscularly injected 2\u2009weeks post\u2013hind limb ischemia establishment (N=4\/group). Improvements were quantified for 4\u2009weeks through walkway gait analysis, contrast angiography, blood pressures, fluorescent microsphere perfusion, and muscle morphology and histology. Capsules remained intact with mesenchymal stromal cells retained for 4\u2009weeks. Adenosine\u2010induced perfusion deficits and muscle atrophy in ischemic limbs were significantly improved by eMSCs versus empty capsules (mean\u00b1SD, 1.07\u00b10.19 versus 0.41\u00b10.16,\n                      <jats:italic>P<\/jats:italic>\n                      =0.002 for perfusion ratios and 2.79\u00b10.12 versus 1.90\u00b10.62\u2009g\/kg,\n                      <jats:italic>P<\/jats:italic>\n                      =0.029 for ischemic muscle mass). Force\u2010 and temporal\u2010associated walkway parameters normalized (ratio, 0.63\u00b10.35 at week 3 versus 1.02\u00b10.19 preligation;\n                      <jats:italic>P<\/jats:italic>\n                      =0.17), and compensatory footfall patterning was diminished in eMSC\u2010administered swine (12.58\u00b18.46% versus 34.85\u00b115.26%;\n                      <jats:italic>P<\/jats:italic>\n                      =0.043). Delivery of eMSCs was associated with trending benefits in collateralization, local neovascularization, and muscle fibrosis. Hypoxia\u2010cultured porcine mesenchymal stromal cells secreted vascular endothelial growth factor and tissue inhibitor of metalloproteinase 2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">This study demonstrates the promise of the mesenchymal stromal cell secretome at improving peripheral artery disease outcomes and the potential for this novel swine model to serve as a component of the preclinical pipeline for advanced therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.123.029880","type":"journal-article","created":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T07:10:49Z","timestamp":1713510649000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Alginate\u2010Encapsulated Mesenchymal Stromal Cells Improve Hind Limb Ischemia in a Translational Swine Model"],"prefix":"10.1161","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6929-6968","authenticated-orcid":false,"given":"Juline N.","family":"Deppen","sequence":"first","affiliation":[{"name":"Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University Atlanta GA"},{"name":"Division of Cardiology Emory University School of Medicine Atlanta GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney C.","family":"Ginn","sequence":"additional","affiliation":[{"name":"Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University Atlanta GA"},{"name":"Division of Cardiology Emory University School of Medicine Atlanta GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8821-266X","authenticated-orcid":false,"given":"Erica O.","family":"Tang","sequence":"additional","affiliation":[{"name":"Division of Cardiology Emory University School of Medicine Atlanta GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanfang","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Cardiology Emory University School of Medicine Atlanta GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2716-2953","authenticated-orcid":false,"given":"Maegan L.","family":"Brockman","sequence":"additional","affiliation":[{"name":"Division of Cardiology Emory University School of Medicine Atlanta GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5405-8716","authenticated-orcid":false,"given":"Rebecca D.","family":"Levit","sequence":"additional","affiliation":[{"name":"Division of Cardiology Emory University School of Medicine Atlanta GA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.318266"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052335"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.314595"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.303565"},{"key":"e_1_3_2_6_2","first-page":"228","article-title":"Intramuscular administration of vascular endothelial growth factor induces dose\u2010dependent collateral artery augmentation in a rabbit model of chronic limb ischemia","volume":"90","author":"Takeshita S","year":"1994","unstructured":"Takeshita S, Pu LQ, Stein LA, Sniderman AD, Bunting S, Ferrara N, Isner JM, Symes JF. 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