Injectable Cardiac ECM Hydrogels Combining With Human Umbilical Mesenchymal Stem Cells Promotes The Recovery Of Myocardial

At present,numerous therapies for acute myocardial ischemia include drugs,percutaneous coronary intervention(PCI)and coronary artery bypass graft(CABG).However,all these treatments can only temporarily attenuate the ischemic tissue,while the impaired cardiac function cannot be restored.Stem cell is a very promising therapy for acute myocardial infarction(AMI),and there have been lots of preclinical experiments to prove that stem cells can promote cardiac repair through directly differentiation into cardiomyocytes and paracrine effects.But the efficacy of cell therapy is still insufficient for the reason of ischemic and anoxic microenvironment.Therefore,the key point is to improve the harsh microenvironment and make it more appropriate for cells surviving.We hypothesized that the injectable pc ECM can provide a three-dimensional space for human umbilical cord mesenchymal stem cells(h UCMSCs),accompanied with necessary nutrition and cytokines.Firstly,we co-cultured pc ECM and h UCMSCs in vitro to detect whether pc ECM can promote the proliferation and viability of h UCMSCs.Then,100 ul PBS,100 ul h UCMSCs,100 ul pc ECM and 100 ul pc ECM/h UCMSCs were respectively transplanted into the left anterior descending artery(LAD)ligated SD rats.All the operated rats were divided into control,h UCMSCs,pc ECM,pc ECM/ h UCMSCs groups.7 and 30 days after operation,LVEF and FS were evaluated by echocardiogram.The heart tissues were sliced into 5?m for HE staining,MASSON staining,immunofluorescence staining to prove the protection of pc ECM/ h UCMSCs for AMI in rats.The results include six parts as follows,1.Co-culturing in vitro: the pc ECM and h UCMSCs were co-cultured with medium and MTT was applied to detect cell survivals at 2,4,6,8 days.Result showed that at 6 and 8 days,the viability of cells in co-culturing group were significantly increased compared with that in control group.2.Echocardiography: LVEF and FS at the baseline and 7 days and 30 days after surgery were respectively detected by small animal ultrasound.LVEF and FS in pc ECM/ h UCMSCs groups were significantly higher than the other groups at 30 days after operation.3.Histology staining: HE and MASSON staining was performed.The fibrosis,infarcted wall thickness and infarcted size of pc ECM/ h UCMSCs group were significantly ameliorated in contrast to those in the other groups.4.?-SMA: compared with the other three groups,angiogenesis in pc ECM/ h UCMSCs were apparently elevated.5.?-MHC: the number of viable myocardial cells in infarcted area was detected by immunofluorescence.The results indicated that pc ECM/ h UCMSCs can accumulate the cardiomyocytes in infarcted area.6.TUNEL: TUNEL kit was applied to detect the number of apoptotic cells in the infarcted area.Results showed that pc ECM/ h UCMSCs may inhibit apoptosis of cells in the infarct area to restore the cardiac function.Our study demonstrated that pc ECM combined h UCMSCs can significantly improve cardiac function and lessen the infarct size in rats.The underlying mechanisms may be the decreased cell apoptosis and increased angiogenesis.