Role of CD44+ Stem Cells in Mural Cell Formation in the Human Choroid: Evidence of Vascular Instability Due to Limited Pericyte Ensheathment
Role of CD44+ Stem Cells in Mural Cell Formation in the Human Choroid: Evidence of Vascular Instability Due to Limited Pericyte Ensheathment
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DOI：
10.1167/iovs.10-5403
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发表时间：
2011-01-01
影响因子：
4.4
通讯作者：
Baxter, Louise
中科院分区：
文献类型：
--
作者：
Chan-Ling, Tailoi;Koina, Mark E.;Baxter, Louise
目的。观察人脉络膜血管形成及成年期的壁细胞分化和周细胞嵌套情况。三、双标记免疫组织化学（α -平滑肌肌动蛋白[α SMA]， desmin, NG2, calponin, caldesmon, CD44， CD34和CD39）应用于人胎儿（妊娠8-32周）和成人脉络膜和视网膜整体和组织学横切片。透射电镜（TEM）检查。发育早期的CD44（+）干细胞也被α - SMA和CD39染色，表明它们有共同的前体。在妊娠12周时，经透射电镜证实，在原始维管树上发现分散和分离的α - SMA（+）壁前细胞。在发育过程中，α - SMA（+）细胞在大小动脉周围形成连续的鞘；静脉中α - SMA表达有间隙。绒毛毛细血管有广泛的血管床，但α - SMA（+）和NG2（+）壁细胞覆盖有限。Calponin仅在大血管上表达，caldesmon未检出。脉络膜成人毛细血管周细胞嵌套率为11%，视网膜为94%。值得注意的是，脉络膜周细胞在TEM上没有可见的中间纤维（IFs），尽管视网膜周细胞中存在中间纤维。视网膜和脉络膜周细胞均未染色。CD44（+）干细胞参与人脉络膜血管壁细胞的形成。人脉络膜血管周细胞套鞘明显减少，提示存在永久打开的“可塑性窗口”，易发生血管不稳定和自身调节能力差。（Invest Ophthalmol Vis Sci. 2011;52:39 -410） DOI:10.1167/iovs.10-5403
PURPOSE. To examine mural cell differentiation and pericyte ensheathment during human choroidal vascular formation and into adulthood.METHODS. Triple-and double-labeled immunohistochemistry (alpha-smooth muscle actin [alpha SMA], desmin, NG2, calponin, caldesmon, CD44, CD34, and CD39) were applied to human fetal (8-32 weeks' gestation) and adult choroidal and retinal wholemounts and histologic cross-sections. Transmission electron microscopy (TEM) was also undertaken.RESULTS. Early in development CD44(+) stem cells also stained with alpha SMA and CD39, suggesting a common precursor. At 12 weeks' gestation, alpha SMA(+) mural precursor cells, confirmed by TEM, were found scattered and isolated over the primordial vascular tree. During development, alpha SMA(+) cells formed a continuous sheath around large arterioles; in veins there were gaps in alpha SMA expression. The choriocapillaris had an extensive vascular bed but limited coverage by alpha SMA(+) and NG2(+) mural cells. Calponin was expressed only on large vessels, and no caldesmon was detected. Pericyte ensheathment of adult capillaries was 11% for choroid versus 94% for retina. Remarkably, choroidal pericytes had no visible intermediate filaments (IFs) on TEM, though IFs were present in retinal pericytes. Neither retinal nor choroidal pericytes stained with desmin.CONCLUSIONS. CD44(+) stem cells are involved in the formation of mural cells in the human choroidal vasculature. A marked reduction in pericyte ensheathment of human choroidal vessels suggests a permanently open "plasticity window" and a predisposition to vascular instability and poor autoregulatory ability. (Invest Ophthalmol Vis Sci. 2011;52:399-410) DOI:10.1167/iovs.10-5403