Prostacyclin Relieves Peripheral Ischemia Through Enhancement of Critical Functions of Hematopoietic Stem Cells
JOURNAL OF CARDIAC FAILURE(2009)
摘要
We have reported that hematopoietic stem cells (HSC) express prostacyclin (PGI2) specific receptor IP, and a deletion of IP in bone marrow (BM) modifies the functions of EPC in vivo and in vitro. To investigate whether PGI2 affects the pathogenesis of peripheral ischemia through HSC functions, we used a mouse model of hindlimb-ischemia (HLI) in which IP was deleted in BM.HSC (lineage-/cKit+/Flk1+ cells) were isolated from BM of wild and IP-deficient (IP-/-) mice. HSC (IP-/-) showed apparent attenuation of properties of adhesion to extra-cellular matrix and cellular migrations. Production of angiogenic cytokines, VEGF, was significantly decreased by 0.45 fold in HSC (IP-/-). Peripheral circulation flow was estimated by laser Doppler image (LDI). As expected, recovery of perfusion flow in HLI of IP-/- mice was apparently reduced compared to wild mice (LDI ratio, 0.29±0.02 versus 0.45±0.03, p<0.05). Transplantation of wild/BM(IP-/-) also demonstrated significant reduction of perfusion flow compared to that of wild/BM(wild) (LDI ratio, 0.29±0.08 versus 0.51±0.07, p<0.05). Moreover, we could rescue the peripheral flow by infusion of wild type HSC.PGI2/IP signal in BM may play an important role for protection system against peripheral ischemia through the enhancement of HSC functions. According to this findings, we have chance to prepare the high performance HSC, and develop the improved cell therapy of peripheral artery diseases.
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关键词
prostacyclin relieves peripheral ischemia,hematopoietic stem cells,hematopoietic stem,stem cells
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