Subretinal transplantation of brain-derived precursor cells to young RCS rats promotes photoreceptor cell survival.

Subretinal transplantation of brain-derived precursor cells to young RCS rats promotes photoreceptor cell survival.
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DOI:
10.1006/exer.2001.1172
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发表时间:
2002-07
影响因子:
3.4
通讯作者:
A. B. Wojciechowski;U. Englund;C. Lundberg;K. Wictorin;K. Warfvinge
A. B. Wojciechowski;U. Englund;C. Lundberg;K. Wictorin;K. Warfvinge
中科院分区:
医学3区
文献类型:
--
作者:
A. B. Wojciechowski;U. Englund;C. Lundberg;K. Wictorin;K. Warfvinge

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体外扩增前体细胞或细胞系在脑修复中的潜在用途包括将这些细胞移植用于细胞替代目的和激活宿主细胞以提供“自我修复”。最近有报道称,从胚胎大鼠髓缝中提取的永生脑源性细胞系RN33B在视网膜下移植到正常成年大鼠后存活、整合和分化。本研究表明,这些细胞移植到出生后21天和35天的正常大鼠和皇家外科学院大鼠视网膜(视网膜变性模型)中,至少可以存活6周。移植细胞整合到视网膜色素上皮和视网膜内层,以及正常和皇家外科学院大鼠视神经的前部。RN33B细胞在视网膜内迁移,从一个偏心点到另一个偏心点占据整个视网膜。大量的移植物细胞分化为胶质细胞,如报告基因LacZ或绿色荧光蛋白的双标记,具有几种胶质标记,包括少突胶质细胞标记。从增殖细胞核抗原和SV40大t抗原免疫组化判断,宿主视网膜内许多移植细胞处于增殖阶段。有趣的是,在皇家外科学院的大鼠中,在出生后21天移植的大鼠中,光感受器的存活率提高了2/3以上的上半球,但在出生后35天没有。此外,在这些大鼠存活的感光层中发现了移植细胞。
The potential use of in vitro-expanded precursor cells or cell lines in brain repair includes transplantation of such cells for cell replacement purposes and the activation of host cells to provide 'self-repair'. Recently, it has been reported that the immortalized brain-derived cell line RN33B (derived from the embryonic rat medullary raphe) survive, integrate and differentiate after subretinal grafting to normal adult rats. Here, it is demonstrated that grafts of these cells survive for at least 6 weeks after implantation into postnatal days 21 and 35 retinas of normal and Royal College of Surgeons rats, a model of retinal degeneration. Implanted cells integrate into the retinal pigment epithelium and the inner retinal layers, and the anterior part of the optic nerve of both normal and Royal College of Surgeons rats. The RN33B cells migrate within the retina, occupying the whole retina from one eccentricity to the other. A significant number of the grafted cells differentiate into glial cells, as shown by the double labelling of the reporter genes LacZ or green fluorescent protein, with several glial markers, including oligodendrocytic markers. Many implanted cells in the host retina were in a proliferative stage judging from proliferative cell nuclear antigen and SV40 large T-antigen immunohistochemistry. Interestingly, there was a promotion of photoreceptor survival, extending over more than 2/3 of the superior hemisphere, in Royal College of Surgeons rats transplanted at postnatal day 21, but not at postnatal day 35. In addition, grafted cells were found in the surviving photoreceptor layer in these rats.