关键词:
1
apoptosis
cell transplantation
heme oxygenase –
mesenchyrnal stern cells
myocardial ischernia
摘要:
Although mesenchymal stem cells (MSCs) have therapeutic potential for tissue injury, intolerance and poor cell viability limit their reparative capability. Therefore, we examined the impact of bone marrowderived MSCs, in which heme oxygenase&3x2013;1 (HO&3x2013;1) was transiently overexpressed, on the repair of an ischemic myocardial injury. When MSCs and HO&3x2013;1&3x2013;overexpressed MSCs (MSC&3x003C;sub&3x003E;H0 &3x2013; 1&3x003C;/sub&3x003E;) were exposed to serum deprivation/hypoxia or H&3x003C;sub&3x003E;2&3x003C;/sub&3x003E;0&3x003C;sub&3x003E;2&3x003C;/sub&3x003E;&3x2013;induced oxidative stress, MSC&3x003C;sub&3x003E;HO &3x2013; 1&3x003C;/sub&3x003E; exhibited increased resistance to cell apoptosis compared with MSCs (17 i; 1 vs. 30 i; 2%, P &3x003C; 0.05) and were markedly resistant to cell death (2 i; 1 vs. 32 i; 2%, P &3x003C; 0.05). Under these conditions, vascular endothelial growth factor (VEGF) production was 2.1&3x2013;fold greater in MSCHO - 1 than in MSCs. Pretreatment of MSCs and MSCHO - 1 with phosphatidylinositol 3&3x2013;kinase (PI 3&3x2013;kinase)/ protein kinase B (Akt) pathway inhibitors such as LY&3x2013;294002 (50 or wortmannin (100 μM) significantly decreased VEGF production. En a rat infarction model with MSCs or MSCHOi (5 X 106 i; 0.1 X 106 cells/rat) transplantation, the number of TdT&3x2013;mediated dUTP nick end&3x2013;labeling&3x2013;positive cells was significantly lower in the MSCHO - 1 group than in the MSC group (i2.i i; i.0 cells/field vs. 26.5 i; 2.6, P &3x003C; 0.05) on the 4th day after cell transplantation. On the 28th day, increased capillary density associated with decreased infarction size was observed in the MSCHO - 1 group (I,415 ± 47/mm2 with 2i.6 i; 2.3%) compared with those in the MSCs group (1,215 i; 43/mm2 with 28.2 i; 2.3%, P &3x003C; 0.05), although infarction size relative to area at risk was not different in each group at 24 h after transplantatio