Theranostic Framework Combining MSC-Derived Extracellular Vesicles and PDGFRβ PET Imaging

Article Impact Level: HIGH
Data Quality: STRONG
Summary of  Cell Stem Cell https://doi.org/10.1016/j.stem.2026.07.003 
Dr. Karl-Henrik Grinnemo  et al.

Points

Uppsala University researchers developed a biological drug using bone marrow mesenchymal stromal cell extracellular vesicles to suppress post-infarction inflammation and cardiac tissue scarring.
Intracoronary administration during balloon angioplasty demonstrated acute cardioprotective effects in swine models and preserved left ventricular function in small-animal ischemic injury trials.
Extracellular vesicles modulate local immune responses by shifting pro-inflammatory cells toward a reparative phenotype that dampens post-ischemic tissue degradation and reduces adverse fibrosis.
Investigators created a companion positron emission tomography tracer targeting platelet-derived growth factor receptor beta to non-invasively visualize active myofibroblast scarring following primary coronary angioplasty.
Human clinical evaluation confirmed that active cardiac myofibroblast activation persists for up to two months post-infarction in specific patients, establishing a clear window for targeted intervention.

Summary

the therapeutic efficacy and diagnostic monitoring of a good manufacturing practice (GMP)-compatible extracellular vesicle (EV)-enriched secretome derived from bone marrow mesenchymal stromal cells (MSCs) for myocardial ischemia-reperfusion (MIR) injury. Despite prompt restoration of coronary blood flow via percutaneous coronary intervention following ST-elevation myocardial infarction (STEMI), adverse fibrotic remodeling frequently leads to heart failure. Led by Karl-Henrik Grinnemo and Olof Eriksson at Uppsala University, researchers evaluated a laminin-521-based production platform to generate MSC EVs for intracoronary delivery during primary angioplasty, paired with novel molecular imaging.

In murine MIR-injury models, EV secretome administration attenuated post-infarction fibrotic remodeling, promoted reparative macrophage polarization, and preserved left ventricular ejection fraction over time. Molecular imaging using a novel platelet-derived growth factor receptor beta (PDGFRβ)-targeted positron emission tomography (PET) tracer demonstrated significant attenuation of PDGFRβ-associated myofibroblast activation compared to untreated controls. Translational efficacy was further confirmed in a clinically relevant porcine ischemia-reperfusion model, where intracoronary EV delivery immediately following reperfusion conferred acute cardioprotection without systemic adverse events.

Clinical translation was established through a novel PDGFRβ-targeted PET platform evaluating longitudinal fibrotic activity in STEMI patients. Serial imaging revealed that active myofibroblast proliferation and scarring persist for up to two months post-STEMI in select patients, identifying a distinct cohort at elevated risk for heart failure. The integrated EV-PET framework establishes a theranostic strategy that pairs anti-inflammatory EV secretome therapy with non-invasive scar monitoring to mitigate adverse remodeling and personalize post-infarction care.

Link to the article: https://www.sciencedirect.com/science/article/pii/S1934590926002638?via%3Dihub

References

Grinnemo, K.-H., Braesch-Andersen, K., Wedin, J. O., Velica, A., Thelander, U., Sabatier, P., Beusch, C. M., Simonson, O. E., Törne, A., Felldin, U., Gritsenko, O., Park, K.-S., Crescitelli, R., Ågren, N., Meinke, S., Abouzayed, A., Wegrzyniak, O., Putri, A., Hedenqvist, P., … Rodin, S. (2026). Extracellular vesicle secretome from mesenchymal stromal cells prevents post-ischemic heart failure by targeting cardiac fibrosis. Cell Stem Cell, S1934590926002638. https://doi.org/10.1016/j.stem.2026.07.003