Aberrant kinetics of bone marrow-derived endothelial progenitor cells in the murine oxygen-induced retinopathy model.
Aberrant kinetics of bone marrow-derived endothelial progenitor cells in the murine oxygen-induced retinopathy model.
复制标题
DOI：
10.1167/iovs.10-5880
复制
发表时间：
2011-10
影响因子：
4.4
通讯作者：
Y. Nakagawa;H. Masuda;Rie Ito;M. Kobori;M. Wada;Tomoko Shizuno;Atsuko Sato;Takahiro Suzuki;K. Kawai;T. Asahara
中科院分区：
文献类型：
--
作者：
Y. Nakagawa;H. Masuda;Rie Ito;M. Kobori;M. Wada;Tomoko Shizuno;Atsuko Sato;Takahiro Suzuki;K. Kawai;T. Asahara
早产儿视网膜病变（Retinopathy of premature，ROP）是一种因氧动力学异常引起的血管病变而导致严重失明的疾病。然而，在ROP的“出生后血管发生”期间骨髓来源的内皮祖细胞（BM来源的EPCs）的系统动力学尚未阐明。因此，作者使用鼠氧诱导视网膜病变（OIR）模型研究了BM衍生的EPCs的动力学。方法C57 BL/6 J小鼠于出生后7 ~ 12天持续通入75%氧气，诱导OIR，随后恢复正常空气环境。结果与对照组相比，流式细胞仪检测的OIR模型中循环EPCs（Sca-1（+）/c-Kit（+）细胞）的频率在高氧相后立即降低（P12），然后在低氧相升高（P17）。此外，BM-Lin（-）/Sca-1（+）（BM-LS）细胞的EPC集落形成测定显示从P12的主要原始EPC集落产生转化为P17的永久EPC集落。在具有EGFP转基因小鼠的BM-LS细胞的BM移植小鼠的OIR视网膜中，在P12时GFP（+）细胞较少掺入血管结构中，而在P17时存在到“簇“和完整血管系统中的剧烈募集。此外，最终EPC集落细胞玻璃体内注射到OIR显着废除病理与原始血管生长。结论：在氧动力学异常的条件下，骨髓源性内皮祖细胞的功能性生物活性发生了变化，这可能为ROP的病理性血管发育提供重要的机制性见解。
PURPOSE Retinopathy of prematurity (ROP) causes serious blindness because of the vasculopathy that results from the abnormal oxygen dynamics. However, the systemic kinetics of bone marrow-derived endothelial progenitor cells (BM-derived EPCs) during the "postnatal vasculogenesis " of ROP has yet to be elucidated. Thus, the authors investigated the kinetics of BM-derived EPCs using a murine oxygen-induced retinopathy (OIR) model. METHODS OIR was induced in C57BL/6J mice by continual aeration with 75% oxygen from postnatal day (P) 7 to P12 that afterward returned to normal room air. RESULTS The frequency of circulating EPCs (Sca-1(+)/c-Kit(+) cells in blood) in an OIR model estimated by FACS decreased immediately after the hyperoxic phase (P12) and then increased at the hypoxic phase (P17) compared with control. Further, EPC colony-forming assay of BM-Lin(-)/Sca-1(+) (BM-LS) cells exhibited a conversion from the predominant primitive EPC colony production at P12 to the definitive EPC colony at P17. In the OIR retinas of BM-transplanted mice with BM-LS cells of EGFP transgenic mice, there was less incorporation of GFP(+) cells into vascular structures at P12, whereas there was a drastic recruitment into the "tufts " and for the intact vasculature at P17. Moreover, the definitive EPC colony cells intravitreally injected into OIR significantly abrogated pathologic versus primitive vascular growth. CONCLUSIONS Taken together, these findings propose that the deviation of functional bioactivities of BM-derived EPCs contributing to intact vascular development under the abnormal oxygen dynamics may provide important mechanistic insight into pathologic vascular development in ROP.