MI ('heart attack') remains the leading cause of heart failure and death in developed-countries. Restoration of cardiac function requires active turnover of damaged heart contracting cells (CM), however, CM endogenous regeneration is not efficient and is a matter of controversy. We show that a bioactive biomaterial alone-decellularized heart tissue (pcECM)-without added cells or growth factors, can elicit a complex regenerative response even after irreversible scarring. The pcECM patch induces macrophage polarization towards constructive remodeling and cardiomyocyte progenitor cell (GATA4(+), c-kit(+)) recruitment (evidenced at both mRNA and protein levels) resulting in de novo immature striated-like muscle patterns (MLC(+), TrpI(+), connexin43(+)). We, therefore, suggest this bioactive pcECM can model cardiac regeneration, and serve as a candidate for fast-track clinical application.

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Background Pericardial effusion is still a common postoperative complication after open heart surgery with cardiopulmonary bypass. Pericardial effusion significantly prolongs the hospital stay and associated costs as well as affecting overall outcomes after open heart surgery in Hanoi Heart Hospital, a tertiary hospital in Vietnam with an annual volume of 1000 patients. This study aimed to investigate the clinical presentation, incidence, and risk factors of postoperative pericardial effusion, which may ensure better prevention of pericardial effusion and improvement in surgical outcomes after open heart surgery. Methods A cross-sectional study was performed on 1127 patients undergoing open heart surgery from January 2015 to December 2015. Results Thirty-six (3.19%) patients developed pericardial effusion. Of these, 16 (44.4%) had cardiac tamponade. Pericardial effusion occurred after valve procedures in 77.8% of cases. Pericardial effusion was detected after discharge in 47.2% of cases at a mean time of 18.1 ± 13.7 days. Univariate logistic regression analysis showed that age> 25 years, body surface area ≥ 1.28 m, preoperative liver dysfunction, New York Heart Association class III/IV, left ventricular end-diastolic diameter z score ≥ 0.55, and postoperative anticoagulant use were associated with postoperative pericardial effusion. Multivariate logistic regression analysis showed that left ventricular end-diastolic diameter z score ≥ 0.55 was an independent risk factor for postoperative pericardial effusion. Conclusions Routine postoperative echocardiography is necessary to detect postoperative pericardial effusion. Increased left ventricular end-diastolic dimension is an independent predictor of postoperative pericardial effusion.

Myocardial restoration using tissue-engineered grafts to regenerate the ischemic myocardium offers improved donor cell retention, yet a limited cell survival resulting from poor vascularization needs to be addressed. A cell type derived from the subamnion, namely, cord-lining mesenchymal stem cells (CL-MSC), has recently been identified. Here we present a restorative strategy that combines a fibrin graft containing human CL-MSC and omental flap providing, thereby, cell-, structural-, and angiogenic support to the injured myocardium. The graft consisted of a mixture of 2 · 10 6 CL-MSC-GFP-Fluc and fibrin. Myocardial infarction (MI) was induced in nude rats and following confirmation of ensued heart failure with echocardiography 2 weeks after injury, therapeutic intervention was performed as follows: untreated (MI, n = 7), CL-MSC graft (CL-MSCG, n = 8), CL-MSCG and omental flap (CL-MSCG + OM, n = 11), and omental flap (OM, n = 8). In vivo bioluminescence imaging at 1, 3, 7, and 14 days post-treatment indicated comparable early donor cell viability between the CL-MSCG and CL-MSCG + OM. Treatment with CL-MSCG + OM improved the myocardial function as assessed by the measurement of end-diastolic left ventricular (LV) pressure (3.53 -0.34 vs. 5.21 -0.54 mmHg, p < 0.05), contractility ( + dP/dt, 3383.8 -250.78 mmHg vs. 2464.9 -191.8 mmHg, p < 0.05), and the relaxation rate (-dP/ dt, -2707.2 -250.7 mmHg vs. 1948.7 -207.8 mmHg, p < 0.05), compared to MI control 6 weeks after ischemic injury. Furthermore, evidence of a 20.32% increase in the ejection fraction was observed in CL-MSCG + OM rats from week 2 to 6 after injury. Both CL-MSCG and CL-MSCG + OM led to an enhanced cardiac output (p < 0.05), and attenuated the infarct size (35.7% -4.2% and 34.7% -4.8%), as compared to MI (60.7% -3.1%; p < 0.01 and p < 0.001, respectively). All treated groups had a higher arteriole density than controls. Yet, a higher amount of functional blood vessels, and a 20-fold increase in arteriole numbers were found in CL-MSCG + OM. Altogether, CL-MSCGs supplemented with vascular supply have the potential to repair the failing, chronically ischemic heart by improving myocardial revascularization, attenuating remodeling, and ameliorating cardiac dysfunction.

A crucial question in post-ischemic cell therapy refers to the ideal method of cell delivery to the heart. We hypothesized that epicardial implantation of subamnion-cord-lining mesenchymal stem cells (CL-MSC) angiogenic spheroids embedded within fibrin grafts (SASG) facilitates donor cell survival and enhances cardiac function in failing rat hearts. Furthermore, we compared the efficacy of this approach applied through two delivery methods. Spheroids made of 1.5 · 10 4 human CL-MSC coated with 2 · 10 3 human umbilical vein endothelial cells were self-assembled in hanging drops. SASG were constructed by embedding 150 spheroids in fibrin matrix. Except for untreated rats (MI, n = 8), grafts were implanted 2 weeks after myocardial infarction upon confirmation of ensued heart failure through thoracotomy: SASG (n = 8) and fibrin graft (FG, n = 8); or video-assisted thoracoscopic surgery (VATS): SASG-VATS (n = 8) and FG-VATS (n = 7). In vivo CL-MSC survival was comparable between both SASG-treated groups throughout the study. SASG and SASG-VATS animals had decreased left ventricular end-diastolic pressure relative to untreated animals, and increased fractional shortening compared to MI and FG controls, 4 weeks after treatment. A 14.1% and 6.2% enhancement in ejection fraction from week 2 to 6 after injury was observed in SASG/SASG-VATS, paralleled by improvement in cardiac output. Treated hearts had smaller scar size, and more blood vessels than MI, while donor CL-MSC contributed to arteriogenesis within the graft and infarct areas. Taken together, our data suggest that SASG treatment has the potential to restore failing hearts by preserving cardiac function and inducing myocardial revascularization, while attenuating cardiac fibrosis. Furthermore, we introduce a method for minimally invasive in situ graft assembly.