Decellularized amniotic membrane attenuates postinfarct left ventricular remodeling

Abstract

BackgroundPlacenta and amnion have been suggested as sources of juvenile cells and tissues for use in surgical regenerative medicine. We previously determined the impact of amniotic epithelial cells induced to undergo epithelial-to-mesenchymal transition (EMT) on myocardial remodeling processes and now evaluated the effects of naïve and processed amniotic membrane (AM) on postischemic left ventricular (LV) geometry and function. MethodsHuman AM was used in unmodified form (AM), after EMT induction by transforming growth factor β (EMT-AM), and after decellularization (Decell-AM). After characterization by histology, electron microscopy, splenocyte proliferation assay, and cytokine release, myocardial infarction was induced in 6–8-week old male BALB/c mice by permanent left anterior descending coronary occlusion, and AM patches were sutured to the anterior LV surface (n = 10 per group). Infarcted hearts without AM or sham-operated mice were used as controls (n = 10 each). After 4 weeks, LV pressure–volume curves were recorded using a conductance catheter before the animals were sacrificed and the hearts analyzed by histology. ResultsTGF-ß treatment induced EMT-like changes in amniotic epithelial cells but increased AM xenoreactivity in vitro (splenocyte proliferation) and in vivo (CD4+ cell invasion). Moreover, in vitro interleukin-6 release from AM and from cardiac fibroblasts co-incubated with AM was 300- or 100-fold higher than that of interleukin-10, whereas Decell-AM did not release any cytokines. AM- and Decell-AM-treated hearts had smaller infarct size and greater infarct scar thickness than infarct control hearts, but there was no difference in myocardial capillary density or the number of TUNEL positive apoptotic cells. LV contractile function was better in the AM and EMT-AM groups than in infarcted control hearts, but dP/dt max, dP/dt min, stroke work, and cardiac output were best preserved in mice treated with Decell-AM. Volume-based parameters (LV end-systolic and end-diastolic volume as well as LV ejection fraction) did not differ between AM and Decell-AM. ConclusionsDecellularized AM supports postinfarct ventricular dynamics independent of the actual regeneration processes. As a cell-free approach to support the infarcted heart, this concept warrants further investigation.