Abstract
Stem cell paracrine activity is implicated in cardiac repair. 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.
Original language | English (US) |
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Pages (from-to) | 1320-1328 |
Number of pages | 9 |
Journal | Stem Cells Translational Medicine |
Volume | 10 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2021 |
Keywords
- cardiopoiesis
- clinomics
- heart failure
- regenerative medicine
- stem cells
- systems biology
- therapy
ASJC Scopus subject areas
- Developmental Biology
- Cell Biology