Objective The effects of cell transplantation on the ischaemic failing heart have already been documented. However, the area in and around infarct regions is not a good environment for cells to survive in because they are exposed to poor conditions in which certain requirements cannot be adequately supplied. We therefore designed a study to investigate the efficacy of transplantation of mesenchymal stem cells with gelatin microspheres containing vascular endothelial growth factor in ischaemic regions.
Methods 12 Chinese mini swines with infarction were randomised into two groups: six swines received autogenetic mesenchymal stem cells (MSCs) to the pefi-infarction area of left ventricular wall (control group), six received mesenchymal stem cell transplantation and gelatin hydrogel microspheres incoporating vascular endothelial growth factor (VEGF-MSCs group). 3 weeks later, left ventricular function was assessed by means of (MRI. The contrast of the MSCs hypointense lesion was determined using the difference in signal intensity between the hypointense and normal myocardium divided by signal intensity of the normal region.
Results The mean diameter of the microspheres is (104±22.6) μm. At 24 h, injection sites of MSCs were identified by MRI as large intramyocardial signal voids that persisted at 3 weeks. Between two groups, there were no significant difference in the contrast of the lesions and in the size of the lesions at 24 h. At 3 weeks after injection, the size of the lesions diminished (p<0.0001) and the contrast of the lesion decreased (p<0.0001). Histology (at 3 weeks) revealed the iron inclusion from Prussian Blue staining matches DAPI fluorescent dyes on adjacent histological sections at ×40 magnification at 3 weeks after MSCs injection, indicating partial ferumoxide particles is still contained within original MSCs. In the MSCs-VEGF microsphere group, the capillary density of the injection site was significantly more than that in MSCs group (42±13.9/HPF vs 29±15.4/HPF, p<0.0001). There were much more dense fluorescently labled MSCs per high power fields in injection sites of MSCs-VEGF microsphere group than that in injection sites of MSCs group (354±83/HPF vs 278±97/HPF, p<0.0001). Moreover, the apoptosis rate of MSCs of MSCs-VEGF microsphere group is more than that of MSCs group (6±4.1)% vs (11±4.8)%, p<0.0001).
Conclusions VEGF incorporated microspheres benefits to the survival of MSCs transplanted to ischaemic myocardium. Microenvironment if one of the most important factors that influence the survival of transplanted MSCs.