The apelin-APJ pathway exists in cardiomyogenic cells derived from mesenchymal stem cells in vitro and in vivo.

Our previous study demonstrated that apelin level increased significantly after the treatment of intracoronary implantation of bone marrow mononuclear cells (BMMCs), followed by the improvement of cardiac function in patients with severe ischemic heart failure. The present studies both in vivo and in vitro explored whether mesenchymal stem cells derived from bone marrow (BMSCs) activate the apelin-APJ pathway when differentiating into cardiomyogenic cells. Isolated BMSCs from rat femurs and tibias were cultured and expanded for three passages, labeled with DAPI, and treated with 5-azacytidine (5-AZ). BMSCs labeled with ad-EGFP were injected intramyocardially into the peri-infarct area of rat models with acute myocardial infarction. Immunofluorescence staining exposed that CMGs expressed apelin together with myogenic-specific proteins such as α-actin, troponin T, GATA-4, and connexin-43 at 7 days after 5-AZ treatment or EGFP-BMSC injection. RT-PCR revealed that mRNA in CMGs started to express apelin and APJ from day 7 and progressively increased until day 28. Cardiac function, as measured by echocardiography in vivo, was significantly improved in parallel with the extent of apelin expression after BMSC transplantation. Our finding indicated that the expression of the apelin-APJ pathway during differentiation of BMSCs into CMGs may be an important mechanism in regulation of myocardial regeneration and functional recovery after BMSC transplantation.

[Autologous mononuclear bone marrow cell transplantation by intracoronary route for patients with ischemic heart disease: observation of 2-years follow-up].

OBJECTIVE: To investigate the long-term effect and safety of intracoronary autologous bone marrow mononuclear cell (BMMC) transplantation in patients with ischemic heart disease (IHD). METHODS: Seventy-six patients with IHD, 26 patients with acute myocardial infarction (AMI) and 26 patients with chronic ischemic heart failure (CIHF), underwent routine treatment plus intracoronary autologous BMMC transplantation, and 24 patients, including 10 patients with AMI and 14 patients with CIHF underwent routine treatment as controls. Autologous BMMC transplantation was performed via a balloon catheter placed into the infarct-related artery during balloon dilatation by high pressure infusion to occlude the artery, which was performed 6 - 8 times for 2 minutes each with 2-minute interval or via a balloon catheter without occluding the infarct-related artery. Follow-up was conducted for 2 years. RESULTS: The surgery was safety without major periprocedural complications. There were no other new arrhythmias found by Holter recorder during the 2-years follow-up. In the AMI patients receiving BNNC transplantation, the left ventricular ejection fraction (LVEF) 1 and 2 years later increased by 5.79% (P < 0.05), 3.79% (P > 0.05) respectively; but there was no change in left ventricular end diastolic volume (LVEDV) and left ventricular end systolic volume (LVESV). The LVEF 1 and 2 years later of the control group increased by 8.8% and 9.2% respectively (both P < 0.01) and the LVESV 1 and 2 years later decreased by 20.4% and 27.8% respectively (both P < 0.05), the myocardium defect area 2 years later was not significantly different from that 3 months later. The heart function of the control group became markedly worse. CONCLUSION: Autologous BMMC intracoronary transplantation is safe and effective, especially in patients with CIHF.

[The autologous bone marrow mononuclear cell transplantation by intracoronary route treat patients with severe heart failure after myocardial infarction].

OBJECTIVE: To investigate the chronic effects of intracoronary autologous bone marrow mononuclear cell (BM-MNCs) transplantation in patients with refractory heart failure (RIHF) after myocardial infarction. METHODS: Thirty patients with RIHF (LVEF < 40%) were enrolled in this nonrandomized study, autologous BM-MNCs (5.0 +/- 0.7) x 10(7) were transplanted with via infarct-related coronary artery in 16 patients and 14 patients received standard medical therapy served as control. Baseline and follow up evaluations included complete clinical evaluations, plasma BNP, ANP, ET-1 measurements, echocardiography, PET, and Holter monitoring. RESULTS: Baseline characteristics were similar between the 2 groups. There were no major periprocedural complications. One patient developed ventricular premature contractions during cell infusion for several seconds and recovered spontaneously. Compared to pre-transplantation, plasma BNP and ET-1 significantly decreased and plasma ANP significantly increased at 7 days post transplantation; 6 minutes walking distance increased from (72.1 +/- 31.5) to (201.6 +/- 23.3) m (P < 0.01), LVEF increased 9.9% (P < 0.001) and FDG-PET revealed vital myocardium area increased (10.3 +/- 3.4)% (P < 0.01) at 3 months after BM-MNCs transplantation. At 6 months follow up, the NYHA class improved from (3.4 +/- 0.1 to 2.4 +/- 0.2, P < 0.001) and no patient died and 1 patient rehospitalized due to lower extremities edema. In control group, LVEF decreased 7.2% compared to baseline (P < 0.001) and was significantly lower than transplantation group at 3 months (P < 0.001). At 6 months follow up, the NYHA class increased from (3.5 +/- 0.1 to 3.9 +/- 0.1, P < 0.05), 2 patients died and 10 patients rehospitalized due to aggravated heart failure. CONCLUSION: Present study demonstrates that intracoronary transplantation of autologous BM-MNCs is safe and effective for treating patients with RIHF after myocardial infarction.