Therapeutic Efficacy Of Mesenchymal Stem Cells (MSC) In The Treatment Of Ischemic Heart Disease

objective MSCs as a novel seed cells for cytological engineering has beengradually approved. But there are still some bottlenecks constraining its clinicalapplication. Among them, the low efficiency of survival and transdifferentiation aftertransplantation and the controversial about the long-term safety and efficacy in clinicalhuman application arouse greater concern. In this study, we try to investigate theinfluence of H₂O₂preconditioning on therapeutic effect of adipose derivedmesenchymal stem cells （ADMSCs） after myocardial infarction. Then, we try toobserve the therapeutic efficiency of human umbilical cord Wharton’s Jellymesenchymal stem cells （WJ-MSCs） transplantation on patients with ischemic cardiacdysfunction.Methods According to the aims mentioned above, this study was divided intotwo parts.First part The concentration of ADMSCs culture supernatant with or without200μM H₂O₂preconditioning was measured.32mice were divided into sham group, MIgroup, ADMSCs group and ADMSCs-H₂O₂group randomly. The mice underwent leftanterior descending coronary artery （LAD） ligation except for the sham group, andreceived injection respectively of phosphate buffered saline （PBS）,1×10⁶ADMSCs, or1×10⁶H₂O₂pretreated ADMSCs via tail vein3hours later. Left ventricularcontractility（LVEDD、LVESD、LVFS） was measured at0,7,14, and28d byechocardiography. After the hearts were excised28days later, cardiac hypertrophyindex was calculated and the average collagen volume fraction （CVF） was analyzed.Second part32patients with ischemic heart dysfunction which were dividedinto treatment group and control group randomly underwent10ml WJ-MSCs（2×10⁷） orsaline transplantation through coronary artery separately. Laboratory tests, ECG, UCGand the MOS item short from health survey （SF-36） were collected before and3,6 months after the transplantation. Main adverse clinical events were recorded.Results1. H₂O₂pretreating increased the secretion of HGF and IL-6by ADMSCssignificantly （P<0.01）. LVESD and LVEDD of ADMSCs-H₂O₂group were much lowerthan that of MI and ADMSCs group（P<0.01）, yet LVFS was much higher （P<0.01）.Cardiac hypertrophy index and CVF of ADMSCs group were notably decreased thanthat of MI group （P<0.01）, which were reduced further in ADMSCs-H₂O₂group（P<0.05）.2. No significant differences were observed in laboratory tests and incidence ofadverse clinical events during the treatment and the follow-up. LVEDV and LVESVwere significantly lower3and6months after transplantation in the treatment groupthan that of before while LVEF was much higher （P<0.05）. There were no significantimprovement in the control group （P>0.05）. The scores of physical functioning andgeneral health notably increased in both groups3and6months after transplantationthan before （P<0.05）, which are significantly higher in the treatment group than that ofthe control group （P<0.05）.Conclusions1. H₂O₂preconditioning augmented paracrine function of ADMSCs in vitro, andenhanced cardiac ventricular contractility as well as reduced myocardial fibrosis in vivo.Therefore, it may be a simple and effective strategy to improve the efficacy ofMSC-based treatments for ischemic heart disease.2. WJ-MSCs transplantation through coronary artery improved cardiac functionand life quality of patients with ischemic heart failure, which may provide a safe andeffective strategy to increase the therapeutic efficiency of MSC-based therapy forischemic heart disease.