Objectives Adipose-derived stem cells (ASCs) have been extensively studied for their therapeutic potential for myocardial infarction (MI). However, the local inflammation and ischaemia induced substantial apoptosis of transplanted ASCs. Statins, HMG-CoA reductase inhibitors, have been shown to suppress inflammation and promote survival of stem cells. This study was designed to investigate whether Rosuvastatin promote ASCs survival and the underlying signal mechanism.
Methods ASCs were isolated from transgenic mice, which were created on the FVB background to constitutively express firefly luciferase and enhanced green fluorescence protein (Fluc-eGFP). Myocardial infarction was created by coronary LAD ligation. ASCs were transplanted into the ischaemic hearts of MI mice with or without Rosuvastatin pretreatment. Transplanted ASCs were tracked by longitudinal bioluminescence imaging. Hypoxia injury (94% N2-5% CO2-1% O2 at 37° for 6 h) was performed to mimic the ischaemic environment of ACSs in vitro. LY294002, the inhibitor of PI3K, was administrated to block the PI3K signal. Apoptosis of ASCs after hypoxia injury was measured by Tunel assay and the expressions of phosphorylated Akt (pAkt) and PI3K were detected by Western blot.
Results The signals of bioluminescence decreased gradually from day 1 to day 21 after transplantation. On day 14 after transplantation, the bioluminescence signals in ASCs with Rosuvastatin group were 2.6 ± 0.25 × 106 photons/s/cm2/sr, while the signals in ASCs group were 4.7 ± 0.6×105 photons/s/cm2/sr (P < 0.05 vs. ASCs + R-tin), which indicated Rosuvastatin promoted the survival and proliferation of ASCs in post-infarct hearts. The administration of Rosuvastatin also significantly inhibited ASCs apoptosis, increased the expressions of PI3K and pAkt in vitro. In contrast, administration of LY294002 blocked the anti-apoptosis effect of Rosuvastatin.
Conclusions Noninvasive imaging could be a valuable tool for monitoring stem cell treatment. Rosuvastatin treatment may improve the survival of implanted ASCs in post-infarct hearts by PI3K-Akt signal pathway.
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