In the past years, cardiac mortality has decreased, but cardiac diseases are still responsible for millions of deaths every year worldwide. Bone-marrow mesenchymal stem cells (BMSCs) transplantation may be a promising therapeutic strategy because of its capacity to differentiate into cardiac cells. Current research indicates that chemical substances, microRNAs, and cytokines have biological functions that regulate the cardiomyocytes differentiation of BMSCs. In this review, we chiefly summarize the regulatory factors that induce BMSCs to differentiate into cardiomyocytes.

The hyperpolarization-activated cyclic nucleotide-gated (HCN) current I_f/I_HCN is generally thought to be carried by Na⁺ and K⁺ under physiological conditions. Recently, Ca²⁺ influx through HCN channels has indirectly been postulated. However, direct functional evidence of Ca²⁺ permeation through I_f/I_HCN is still lacking. To possibly provide direct evidence of Ca²⁺ influx through I_HCN/I_f, we performed inside-out and cell-attached single-channel recordings of heterologously expressed HCN channels and native rat and human I_f, since Ca²⁺-mediated I_f/I_HCN currents may not readily be recorded using the whole-cell technique. Original current traces demonstrated HCN2 Ca²⁺ inward currents upon hyperpolarization with a single-channel amplitude of −0.87 ± 0.06 pA, a low open probability of 3.02 ± 0.48% (at −110 mV, n = 6, Ca²⁺ 2 mmol/L), and a Ca²⁺ conductance of 8.9 ± 1.2 pS. I_HCN2-Ca2+ was significantly activated by the addition of cAMP with an increase in the open probability and suppressed by the specific I_f inhibitor ivabradine, clearly confirming that Ca²⁺ influx indeed was conducted by HCN2 channels. Changing [Na⁺] (10 vs. 100 mmol/L) in the presence or absence of 2 mmol/L Ca²⁺ caused a simple shift of the reversal potential along the voltage axis without significantly affecting Na⁺/Ca²⁺ conductance, whereas the K⁺ conductance of HCN2 increased significantly in the absence of external Ca²⁺ with increasing K⁺ concentrations. The mixed K⁺–Ca²⁺ conductance, however, was unaffected by the external K⁺ concentration. Notably, we could also record hyperpolarization-activated Ca²⁺ permeation of single native I_f channels in neonatal rat ventriculocytes and human atrial myocytes in the presence of blockers for all known cardiac calcium conduction pores (Ca²⁺ conductance of human I_f, 9.19 ± 0.34 pS; amplitude, −0.81 ± 0.01 pA; open probability, 1.05 ± 0.61% at −90 mV). We directly show Ca²⁺ permeability of native rat and, more importantly, human I_f at physiological extracellular Ca²⁺ concentrations at the physiological resting membrane potential. This might have particular implications in diseased states with increased I_f density and HCN expression.

ST-elevation myocardial infarction (STEMI) is one of the main reasons for morbidity and mortality worldwide. In addition to the classic biomarker NT-proBNP, new biomarkers like ST2 and Pentraxin-3 (Ptx-3) have emerged as potential tools in stratifying risk in cardiac patients. Indeed, multimarker approaches to estimate prognosis of STEMI patients have been proposed and their potential clinical impact requires investigation. In our study, in 147 patients with STEMI, NT-proBNP as well as serum levels of ST2 and Ptx-3 were evaluated. During two-year follow-up (FU; 734.2 ± 61.2 d) results were correlated with risk for cardiovascular mortality (CV-mortality). NT-proBNP (HR = 1.64, 95% CI = 1.21–2.21, p = 0.001) but also ST2 (HR = 1.000022, 95% CI = 1.00–1.001, p < 0.001) were shown to be reliable predictors of CV-mortality, while the highest predictive power was observed with Ptx-3 (HR = 3.1, 95% CI = 1.63–5.39, p < 0.001). When two biomarkers were combined in a multivariate Cox regression model, relevant improvement of risk assessment was only observed with NT-proBNP+Ptx-3 (AIC = 209, BIC = 214, p = 0.001, MER = 0.75, MEV = 0.64). However, the highest accuracy was seen using a three-marker approach (NT-proBNP + ST2 + Ptx-3: AIC = 208, BIC = 214, p < 0.001, MER = 0.77, MEV = 0.66). In conclusion, after STEMI, ST2 and Ptx-3 in addition to NT-proBNP were associated with the incidence of CV-mortality, with multimarker approaches enhancing the accuracy of prediction of CV-mortality.