Retinal cells integrate into the outer nuclear layer and differentiate into mature photoreceptors after subretinal transplantation into adult mice
Retinal cells integrate into the outer nuclear layer and differentiate into mature photoreceptors after subretinal transplantation into adult mice
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DOI：
10.1016/j.exer.2008.01.018
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发表时间：
2008-04-01
影响因子：
3.4
通讯作者：
Ader, Marius
中科院分区：
文献类型：
--
作者：
Bartsch, Udo;Oriyakhel, Wasi;Ader, Marius
由光感受器变性引起的视力障碍，被称为视网膜色素变性，是一种使人衰弱的疾病，目前尚无治愈方法。以细胞为基础的治疗方法是替代退化或丢失的光感受器的一种治疗选择。本研究评估了新生小鼠视网膜原代细胞移植入成年小鼠外核层（ONL）并分化为成熟光感受器的潜力。在出生后(P) 0、P1或P4天，从普遍表达增强绿色荧光蛋白（EGFP）的转基因小鼠的视网膜中分离视网膜细胞，并将其移植到成年野生型小鼠的视网膜下空间。移植后1周至11个月分析实验视网膜供体细胞的整合和分化情况。免疫组织化学和电镜证实，移植后，一些出生后的视网膜细胞融入宿主的ONL，并分化为成熟的光感受器，包括内段和外段。值得注意的是，egfp阳性光感受器的出现并不是供体细胞与内源性光感受器融合的结果。与P0或P1分离的细胞相比，P4分离的视网膜细胞融入ONL和分化为成熟光感受器的能力显著增加。由于P4分离的细胞悬液富集于杆状光感受器细胞命运的细胞，因此我们很容易推测，未成熟的光感受器可能具有最高的整合和分化潜力，因此可能是一种有希望的细胞类型，可以为涉及杆状光感受器丧失的疾病制定细胞替代策略。(C) 2008 Elsevier Ltd版权所有。
Vision impairment caused by degeneration of photoreceptors, termed retinitis pigmentosa, is a debilitating condition with no cure presently available. Cell-based therapeutic approaches represent one treatment option by replacing degenerating or lost photoreceptors. In this study the potential of transplanted primary retinal cells isolated from neonatal mice to integrate into the outer nuclear layer (ONL) of adult mice and to differentiate into mature photoreceptors was evaluated. Retinal cells were isolated from retinas of transgenic mice ubiquitously expressing enhanced green fluorescence protein (EGFP) at either postnatal day (P) 0, P1 or P4 and transplanted into the subretinal space of adult wild-type mice. One week to 11 months post-transplantation experimental retinas were analyzed for integration and differentiation of donor cells. Subsequent to transplantation some postnatal retinal cells integrated into the ONL of the host and differentiated into mature photoreceptors containing inner and outer segments as confirmed by immunohistochemistry and electron microscopy. Notably, the appearance of EGFP-positive photoreceptors was not the result of fusion between donor cells and endogenous photoreceptors. Retinal cells isolated at P4 showed a significant increase in their capacity to integrate into the ONL and to differentiate into mature photoreceptors when compared with cells isolated at P0 or P1. As cell suspensions isolated at P4 are enriched in cells committed towards a rod photoreceptor cell fate it is tempting to speculate that immature photoreceptors may have the highest integration and differentiation potential and thus may present a promising cell type to develop cell replacement strategies for diseases involving rod photoreceptor loss. (C) 2008 Elsevier Ltd. All rights reserved.