Pericardial Transplantation Of Preconditioned Cardiospheres To Treat Acute Myocardial Infarction In Rats

Objective:In order to transplant cardiospheres(CSps)with favorable stemness and superior secretion function for myocardial infarction therapy,the present study aimed to explore the feasibility of CSps pre-stimulated culture.And the study also attempted to establish a pericardial cavity transplantation route in the rat acute myocardial infarction model and studied the therapeutic effects and relative regenerative mechanisms of CSps on myocardial infarction.Methods:CSps was isolated and cultured from the rat heart tissue,immunofluorescence staining was performed to detect the expression of cardiac stem cell markers.Different concentrations of pericardial effusion after myocardial infarction(PFMI)were used to pre-stimulate CSps,and q PCR assays were used to examine the expression levels of stem cell markers,c Tn T,and growth factors.Using phosphate buffer as control,Matrigel was used to mix with CSps,and both cell viabilities and growth factor levels were examined.The rat acute myocardial infarction model was established by the ligation of the left anterior descending coronary artery,the mixture of Matrigel and CSps were injected into the rat pericardial cavity,the cardiac function was monitored for four weeks,and both the CSps survival and cardiac regeneration were observed.Results:In vitro,the three-dimensional spherical growth CSps was obtained,and pre-stimulated treatments of 50% PFMI significantly increased the levels of cardiac stem genes(c-kit,KDR,Sca-1),cardiomyocytes(c Tn T),and growth factors(VEGF,b FGF,HGF,and IGF-1)in CSps.The Matrigel successfully protected the viabilities of CSps in vitro.In the MI model,CSps was transplanted in the pericardial cavity,and it significantly improved the cardiac function and reduced infarcted size.16.8% of CSps survived four weeks following transplantation,and the content of VEGF,b FGF,HGF,and IGF-1 in pericardial cavity significantly increased.Both cardiac regeneration and angiogenesis were observed within the infarcted area.Conclusion:CSps with favorable stemness and superior secretion functions were obtained by using pre-stimulated treatments,and transplanting CSps matrix hydrogel suspension into the pericardial cavity significantly protected the myocardial infarction cardiac function,reduced infarcted size,and improved the cardiac regeneration and angiogenesis within the infarcted area.