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骨髓间充质干细胞视网膜下移植可延缓视网膜色素变性RCS大鼠模型的视网膜变性。

Subretinal transplantation of bone marrow mesenchymal stem cells delays retinal degeneration in the RCS rat model of retinal degeneration.

作者信息

Inoue Yuji, Iriyama Aya, Ueno Shuji, Takahashi Hidenori, Kondo Mineo, Tamaki Yasuhiro, Araie Makoto, Yanagi Yasuo

机构信息

Department of Ophthalmology, University of Tokyo School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

出版信息

Exp Eye Res. 2007 Aug;85(2):234-41. doi: 10.1016/j.exer.2007.04.007. Epub 2007 May 6.

Abstract

Because there is no effective treatment for this retinal degeneration, potential application of cell-based therapy has attracted considerable attention. Several investigations support that bone marrow mesenchymal stem cells (MSCs) can be used for a broad spectrum of indications. Bone marrow MSCs exert their therapeutic effect in part by secreting trophic factors to promote cell survival. The current study investigates whether bone marrow MSCs secrete factor(s) to promote photoreceptor cell survival and whether subretinal transplantation of bone marrow MSCs promotes photoreceptor survival in a retinal degeneration model using Royal College of Surgeons (RCS) rats. In vitro, using mouse retinal cell culture, it was demonstrated that the conditioned medium of the MSCs delays photoreceptor cell apoptosis, suggesting that the secreted factor(s) from the MSCs promote photoreceptor cell survival. In vivo, the MSCs were injected into the subretinal space of the RCS rats and histological analysis, real-time RT-PCR and electrophysiological analysis demonstrated that the subretinal transplantation of MSCs delays retinal degeneration and preserves retinal function in the RCS rats. These results suggest that MSC is a useful cell source for cell-replacement therapy for some forms of retinal degeneration.

摘要

由于目前尚无针对这种视网膜变性的有效治疗方法,基于细胞的治疗的潜在应用已引起了广泛关注。多项研究表明,骨髓间充质干细胞(MSCs)可用于多种适应症。骨髓间充质干细胞部分通过分泌营养因子来促进细胞存活,从而发挥其治疗作用。本研究旨在探讨骨髓间充质干细胞是否分泌促进光感受器细胞存活的因子,以及在使用皇家外科医学院(RCS)大鼠的视网膜变性模型中,骨髓间充质干细胞的视网膜下移植是否能促进光感受器的存活。在体外,通过小鼠视网膜细胞培养证明,间充质干细胞的条件培养基可延迟光感受器细胞凋亡,这表明间充质干细胞分泌的因子能促进光感受器细胞存活。在体内,将间充质干细胞注入RCS大鼠的视网膜下间隙,组织学分析、实时RT-PCR和电生理分析表明,间充质干细胞的视网膜下移植可延缓RCS大鼠的视网膜变性并保留其视网膜功能。这些结果表明,间充质干细胞是某些形式视网膜变性细胞替代治疗的有用细胞来源。

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