Cited 6 times since 2016 (1.1 per year) source: Scopus PloS one, Volume 11, Issue 4, 6 1 2016, Pages e0152938 Discrepant Results of Experimental Human Mesenchymal Stromal Cell Therapy after Myocardial Infarction: Are Animal Models Robust Enough? den Haan MC, van Zuylen VL, Pluijmert NJ, Schutte CI, Fibbe WE, Schalij MJ, Roelofs H, Atsma DE

Background

Human mesenchymal stromal cells (MSCs) have been reported to preserve cardiac function in myocardial infarction (MI) models. Previously, we found a beneficial effect of intramyocardial injection of unstimulated human MSCs (uMSCs) on cardiac function after permanent coronary artery ligation. In the present study we aimed to extend this research by investigating the effect of intramyocardial injection of human MSCs pre-stimulated with the pro-inflammatory cytokine interferon-gamma (iMSCs), since pro-inflammatory priming has shown additional salutary effects in multiple experimental disease models.

Methods

MI was induced in NOD/Scid mice by permanent ligation of the left anterior descending coronary artery. Animals received intramyocardial injection of uMSCs, iMSCs or PBS. Sham-operated animals were used to determine baseline characteristics. Cardiac performance was assessed after 2 and 14 days using 7-Tesla magnetic resonance imaging and pressure-volume loop measurements. Histology and q-PCR were used to confirm MSC engraftment in the heart.

Results

Both uMSC and iMSC therapy had no significant beneficial effect on cardiac function or remodelling in contrast to our previous studies.

Conclusions

Animal models for cardiac MSC therapy appear less robust than initially envisioned.

PLoS One. 2016 4;11(4):e0152938