Objective This study was designed to evaluate the contribution of apelin to the therapeutic efficacy of mesenchymal stem cells in hindlimb ischaemia mice.
Methods Mesenchymal stem cells (MSC) expressing firefly luciferase (Fluc) were isolated from ß-actin-luc mice and characterised by flow cytometry and bioluminescence imaging (BLI). Male FVB mice underwent femoral artery ligation and received MSC (1×106) or MSC with Apelin intra-quadriceps femoris muscle injection. Cell survival was imaged by BLI. Angiogenesis was assessed by immunohistochemisty method. The expressions of AKT and pAKT after cellular therapy were analysed by Western blot.
Results Fluc expression correlated with cell number in all groups. In vivo BLI revealed acute donor cell death of MSC within 2 weeks after transplantation. By contrast, signals of injected cells were still present after 4 weeks in the MSC with apelin group. Immunohistochemisty showed more angiogenesis in the MSC with Apelin group compared to MSC (p<0.05). In vitro apelin treatment of MSC exposed to hypoxia increased cell proliferation. Moreover, considerable increases in phosphorylation of Akt were found in MSC pretreated with apelin.
Conclusions Apelin has beneficial effects on the therapeutic efficacy and survival maintenance of mesenchymal stem cells in hindlimb ischaemia and might constitute an important therapy target in cardiovascular disease.
- molecular imaging
- mesenchymal stem cells