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Linkage between secretome functionality and therapeutic outcome was here interrogated by systems analytics of biobanked human cardiopoietic cells, a regenerative biologic in advanced clinical trials. Protein chip array identified 155 proteins differentially secreted by cardiopoietic cells with clinical benefit, expanded into a 520 node network, collectively revealing inherent vasculogenic properties along with cardiac and smooth muscle differentiation and development. Next generation RNA sequencing, refined by pathway analysis, pinpointed miR-146 dependent regulation upstream of the decoded secretome. Intracellular and extracellular integration unmasked commonality across cardio-vasculogenic processes. Mirroring the secretome pattern, infarcted hearts benefiting from cardiopoietic cell therapy restored the disease proteome engaging cardiovascular system functions. The cardiopoietic cell secretome thus confers a therapeutic molecular imprint on recipient hearts, with response informed by predictive systems profiling.<\/jats:p>","DOI":"10.1002\/sctm.20-0509","type":"journal-article","created":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T13:09:25Z","timestamp":1622207365000},"page":"1320-1328","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Secretome Signature of Cardiopoietic Cells Echoed in Rescued infarcted Heart Proteome"],"prefix":"10.1093","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2934-3782","authenticated-orcid":false,"given":"D. 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