Wang Shaomei, Lu Bin, Wood Patrick, Lund Raymond D
John A. Moran Eye Center, University of Utah Health Science Center, Salt Lake City, Utah 84132, USA.
Invest Ophthalmol Vis Sci. 2005 Jul;46(7):2552-60. doi: 10.1167/iovs.05-0279.
To study the distribution of the human retinal pigment epithelium (hRPE) cell line ARPE-19 and human Schwann (hSC) cells grafted to the subretinal space of the Royal College of Surgeon (RCS) rat and the relation of graft cell distribution to photoreceptor rescue.
Cell suspensions of both donor types were injected into the subretinal space of 3-week-old dystrophic RCS rats through a transscleral approach, human fibroblast and medium were used as control grafts. All animals were maintained on oral cyclosporine. At 1, 2, 4, 6, 15, 28, and 36 weeks after grafting, animals were killed. Human cell-specific markers were used to localize donor cells.
Both donor cell types, as revealed by antibodies survived for a substantial time. Their distribution was very different: hRPE cells formed a large clump early on and, with time, spread along the host RPE in a layer one to two cells deep, whereas hSCs formed many smaller clumps, mainly in the subretinal space. Both cells rescued photoreceptors beyond the area of donor cell distribution. The number of surviving cells declined with time.
Both hRPE and hSC grafts can survive and rescue photoreceptors for a substantial time after grafting. The number of both donor cell types declined with time, which could be an immune-related problem and/or due to other factors intrinsic to the host RCS retina. The fact that rescue occurred beyond the area of donor cell distribution suggests that diffusible factors are involved, raising the possibility that the two cell types function in a similar manner to rescue photoreceptors.
研究人视网膜色素上皮(hRPE)细胞系ARPE - 19和人雪旺氏(hSC)细胞移植到皇家外科医学院(RCS)大鼠视网膜下间隙后的分布情况,以及移植细胞分布与光感受器挽救之间的关系。
通过经巩膜途径将两种供体细胞悬液注入3周龄营养不良的RCS大鼠的视网膜下间隙,用人成纤维细胞和培养基作为对照移植物。所有动物均口服环孢素。在移植后1、2、4、6、15、28和36周处死动物。使用人细胞特异性标记物定位供体细胞。
两种供体细胞类型经抗体检测均存活了相当长的时间。它们的分布差异很大:hRPE细胞早期形成一个大的细胞团,随着时间推移,沿宿主RPE呈一到两层细胞深的层状扩散,而hSCs形成许多较小的细胞团,主要位于视网膜下间隙。两种细胞均在供体细胞分布区域之外挽救了光感受器。存活细胞数量随时间下降。
hRPE和hSC移植物在移植后均可存活并在相当长的时间内挽救光感受器。两种供体细胞类型的数量均随时间下降,这可能是一个免疫相关问题和/或由于宿主RCS视网膜的其他内在因素。在供体细胞分布区域之外发生挽救这一事实表明涉及可扩散因子,这增加了两种细胞类型以类似方式发挥作用来挽救光感受器的可能性。