{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:01:16Z","timestamp":1792450876612,"version":"4.5.0"},"reference-count":28,"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":[[2026,5,5]]},"abstract":"\n Background<\/jats:title>\n In ischemic heart failure, the biological mechanisms underlying the benefits of mesenchymal stromal cells (MSCs) and c\u2010kit\u2013positive cardiac progenitor cells (CPCs) remain incompletely understood.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n In this predefined secondary biomarker analysis of 96 patients from the multicenter, randomized, double\u2010blind, placebo\u2010controlled Cardiovascular Cell Therapy Research Network CONCERT\u2010HF (Combination of Mesenchymal and c\u2010Kit+ Cardiac Stem Cells as Regenerative Therapy for Heart Failure) trial, plasma biomarkers were measured at baseline and at days 7, 30, and 180. Changes were assessed using 2\u2010sample randomization median tests and multivariate 2\u2010sample Cram\u00e9r\u2013von Mises tests to evaluate time point\u2013specific and trajectory\u2010level effects. Complementary longitudinal mixed\u2010effects models were used to assess treatment\u00d7time interactions.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Cell therapy induced distinct, time\u2010dependent biomarker changes. Significant reductions were observed in TRAIL\u2010R1 (tumor necrosis factor receptor superfamily member 10A; MSCs+CPCs), IL\u201033 (interleukin\u201033), and GDF\u201015 (growth differentiation factor 15; MSCs, CPCs), PTX3 (pentraxin 3; MSCs, and MSCs+CPCs), TNF\u2010\u03b1 (tumor necrosis factor\u2010alpha; MSCs and MSCs+CPCs), and PDGF\u2010BB (platelet\u2010derived growth factor\u2010BB; all cell therapy groups). VEGF\u2010A (vascular endothelial growth factor A), HGF (hepatocyte growth factor), and BMP\u20109 (bone morphogenetic protein 9) also decreased significantly in the MSCs cohort. Multivariate 2\u2010sample Cram\u00e9r\u2013von Mises test confirmed significant treatment\u2010related shifts in biomarker trajectories for PTX3, TNF\u2010\u03b1, PDGF\u2010BB, GDF\u201015, BMP\u20109, and MMP\u20101 (matrix metalloproteinase\u20101). Complementary longitudinal mixed\u2010effects modeling demonstrated significant treatment\u00d7time interactions for TNF\u2010\u03b1, MMP\u20101, and BMP\u20109. Among individual contrasts, PDGF\u2010BB showed the most consistent treatment effect, including a reduction in the MSCs group versus placebo at day 30 (estimate, \u2212157.98 [95% CI, \u2212286.04 to \u221229.91];\n P<\/jats:italic>\n =0.01). Time\u2010specific treatment contrasts for most other biomarkers were modest with wide CIs. Greater increases in PDGF\u2010BB at day 180 were associated with smaller improvements in Minnesota Living With Heart Failure Questionnaire scores.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n MSCs, CPCs, and their combination are associated with selective, time\u2010dependent modulation of inflammatory and matrix remodeling biomarkers in ischemic heart failure. These findings provide mechanistic insight into cell therapy effects and identify PDGF\u2010BB, PTX3, TNF\u2010\u03b1, MMP\u20101, and BMP\u20109 as candidate biomarkers for response monitoring and hypothesis generation in future regenerative trials.<\/jats:p>\n <\/jats:sec>\n \n Registration<\/jats:title>\n \n URL:\n https:\/\/clinicaltrials.gov<\/jats:ext-link>\n ; Unique Identifier: NCT02501811.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.125.045963","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T09:58:49Z","timestamp":1776679129000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Changes in Circulating Biomarkers in Patients With Ischemic Heart Failure After Treatment With Autologous Mesenchymal Stromal Cells and c\u2010Kit\u2010Positive Cardiac Cells, Alone or in Combination: Results From the Cardiovascular Cell Therapy Research Network CONCERT\u2010HF Clinical Trial"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3957-4717","authenticated-orcid":false,"given":"Lourdes","family":"Chacon\u2010Alberty","sequence":"first","affiliation":[{"name":"Texas Heart Institute at Baylor College of Medicine","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Tan","sequence":"additional","affiliation":[{"name":"Rice University","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2123-2444","authenticated-orcid":false,"given":"Meng","family":"Li","sequence":"additional","affiliation":[{"name":"Rice University","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5987-340X","authenticated-orcid":false,"given":"Xian\u2010Liang","family":"Tang","sequence":"additional","affiliation":[{"name":"University of Louisville","place":["Louisville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1425-594X","authenticated-orcid":false,"given":"Camila","family":"Hochman\u2010Mendez","sequence":"additional","affiliation":[{"name":"Texas Heart Institute at Baylor College of Medicine","place":["Houston, USA"]},{"name":"Biofluids Repository Core, Advanced Technology Core, Baylor College of Medicine","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9160-8614","authenticated-orcid":false,"given":"Roberto","family":"Bolli","sequence":"additional","affiliation":[{"name":"University of Louisville","place":["Louisville, 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