HUMAN EMBRYONIC RETINAL CELL TRANSPLANTS IN ATHYMIC IMMUNODEFICIENT RAT HOSTS
HUMAN EMBRYONIC RETINAL CELL TRANSPLANTS IN ATHYMIC IMMUNODEFICIENT RAT HOSTS
复制标题
DOI：
10.1177/096368979400300603
复制
发表时间：
1994-11-01
影响因子：
3.3
通讯作者：
SEILER, MJ
中科院分区：
文献类型：
--
作者：
ARAMANT, RB;SEILER, MJ
本研究探讨了利用胸腺“裸”大鼠作为无免疫抑制的人胚胎视网膜细胞移植宿主的可能性。这种移植的长期发展与我们早期使用免疫抑制大鼠的研究结果进行了比较，并显示出对s抗原的移植免疫反应性。其他一些细胞标志物包括：视紫红质、杆α -转导素、神经元特异性烯醇化酶（NSE）、突触蛋白（SYN）、锥体特异性视蛋白、vimentin、细胞视黄醛结合蛋白（CRALBP）、胶质纤维酸性蛋白（GFAP）、大鼠主要组织相容性抗原II类（MHC-II）和大鼠巨噬细胞标志物（Ox-42）。将人视网膜细胞（9-13周）移植到28只胸腺大鼠眼内。宿主大鼠术后在微隔离笼中饲养48周。采用组织学、免疫组织化学和电镜技术研究了移植物的宿主免疫反应和发育。当使用受孕后9-11周的供体视网膜时，35只眼睛中有31只的移植体直径长到2-3毫米，并有许多玫瑰花结。从受孕后12-13周的供体中获得的移植不能很好地存活（11只眼睛中有8只），更小，组织更差。所有移植体与宿主视网膜融合良好，优于免疫抑制大鼠宿主的相应移植体。即使在很长的存活时间后，大多数移植物似乎是健康的，只有偶尔在移植物或宿主视网膜中观察到MHC-II阳性巨噬细胞。除玻璃体表面的内限定膜外，其余视网膜各层均观察到。年龄最大的移植体（34-57周总年龄=供体年龄+术后时间）表现出发育良好的光感受器、杆状体和锥状体，有内节和外节。syn染色显示内、外网状层发育。虽然许多视锥细胞对SYN和NSE染色，但很少有红绿或蓝视蛋白免疫反应。大多数视杆细胞对s抗原和视紫红质产生免疫反应。移植Muller细胞进行vimentin和CRALBP染色。GFAP的免疫反应性发展缓慢，直到44周龄才在所有移植Muller细胞中完全表达。裸鼠为研究人类视网膜异种移植提供了一个良好的模型，没有免疫抑制的负面影响。与免疫抑制大鼠相比，裸鼠移植结果一致，宿主和移植体的长期存活率更高。
This study investigates the possibility to use the athymic ''nude'' rat as a host for the transplantation of human embryonic retinal cells without immunosuppression. The long-term development of such transplants is compared with results from our earlier study that used immunosuppressed rats, and showed transplant immunoreactivity for S-antigen. Several additional cell markers have been included: rhodopsin, rod (alpha-transducin, neuron-specific enolase (NSE), synaptophysin (SYN), cone-specific opsins, vimentin, cellular retinaldehyde binding protein (CRALBP), glial fibrillary acidic protein (GFAP), rat major histocompatibility antigen class II (MHC-II) and a rat macrophage marker (Ox-42). Human retinal cells (9-13 wk postconception) were transplanted to the eyes of 28 athymic rats. Host rats mere kept in microisolator cages for up to 48 wk after surgery. Host immune response and the development of the transplants mere studied using histology, immunohistochemistry and electron microscopy. When using retinas of donors 9-11 wk postconception, transplants grew to 2-3 mm in diameter with many rosettes, in 31 of 35 eyes. Transplants derived from donors 12-13 wk postconception did not survive as well (8 out of 11 eyes), were smaller and less organized. All transplants fused well with the host retina, better than corresponding transplants to immunosuppressed rat hosts. Most transplants appeared to be healthy, even after long survival times, and only occasionally were MHC-II positive macrophages observed in transplants or host retinas. All retinal layers were observed, except for an inner limiting membrane on the vitreous surface. The oldest transplants (34-57 wk total age = donor age + time after surgery) exhibited well developed photoreceptors, rods and cones, with inner and outer segments. SYN-staining showed the development of inner and outer plexiform layers. Although many cones stained for SYN and NSE, few were immunoreactive for red-green or blue opsin. Most rods became immunoreactive for S-antigen and rhodopsin. Transplant Muller cells stained for vimentin and CRALBP. Immunoreactivity for GFAP developed slowly and was not completely expressed in all transplant Muller cells until 44 wk total age. Nude rats offer an excellent model for the study of human retinal xenografts without the negative effects of immunosuppression. Compared to immunosuppressed rats, transplantation to nude rats gives consistent results and superior long-term survival of hosts and transplants.