A comparison of neural differentiation and retinal transplantation with bone marrow-derived cells and retinal progenitor cells
A comparison of neural differentiation and retinal transplantation with bone marrow-derived cells and retinal progenitor cells
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DOI：
10.1634/stemcells.2005-0507
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发表时间：
2006-10-01
期刊：
影响因子：
5.2
通讯作者：
Young, Michael J.
中科院分区：
文献类型：
--
作者：
Tomita, Minoru;Mori, Taisuke;Young, Michael J.
视网膜祖细胞（RPC）是不成熟的前体细胞，可以分化为视网膜神经元，包括光感受器。最近，据报道，骨髓来源的细胞也可能能够分化为中枢神经系统谱系的细胞，包括视网膜神经元。我们比较了这两种细胞类型，以评估它们作为视网膜移植细胞来源的潜力。从增强型绿色荧光蛋白小鼠中分离出骨髓基质细胞（MSC）和巨噬细胞。 MSCs与脑源性神经营养因子、神经生长因子和碱性成纤维细胞生长因子一起培养以诱导神经元分化。 RPCs在相同条件下或用10%胎牛血清培养。检查并比较 MSC 和 RPC 之间的神经元标志物表达。 MSC、巨噬细胞和 RPC 也与视紫红质敲除小鼠的移植视网膜一起培养，以研究它们视网膜整合的潜力。通过逆转录聚合酶链反应和免疫细胞化学，MSC 表达神经元和视网膜特异性标记物。两种类型的细胞均迁移至视网膜外植体中并表达神经丝200、神经胶质原纤维酸性蛋白、蛋白激酶C-a和恢复蛋白。 RPC 表达视紫红质，这是一种我们从未在 MSC 中检测到的光感受器标记物。在移植的视网膜中，大多数骨髓来源的巨噬细胞分化成类似于小胶质细胞的细胞，而不是神经细胞。这项研究表明，与 MSC 相比，RPC 可能是视网膜移植研究的首选细胞类型。然而，间充质干细胞可能仍然是自体移植的有吸引力的候选者。
Retinal progenitor cells (RPCs) are immature precursors that can differentiate into retinal neurons, including photoreceptors. Recently, it has been reported that bone marrow-derived cells may also be capable of differentiation into cells of central nervous system lineage, including retinal neurons. We compared these two cell types to evaluate their potential as, a source of cells for retinal transplantation. Marrow stromal cells (MSCs) and macrophages were isolated from enhanced green fluorescence protein mice. MSCs were cultured with brain-derived neurotrophic factor, nerve growth factor, and basic fibroblast growth factor to induce neuronal differentiation. RPCs were cultured under the same conditions or with 10% fetal bovine serum. Neuronal marker expression was examined and compared between MSCs and RPCs. MSCs, macrophages, and RPCs were also cultured with explanted retinas from rhodopsin knockout mice to study their potential for retinal integration. MSCs expressed neuronal and retina-specific markers by reverse transcription-polymerase chain reaction and immunocytochemistry. Both types of cells migrated into retinal explants and expressed neurofilament 200, glial fibrillary acidic protein, protein kinase C-a, and recoverin. RPCs expressed rhodopsin, a photoreceptor marker we never detected in MSCs. A majority of bone marrow derived-macrophages differentiated into cells that resembled microglia, rather than neural cells, in the explanted retina. This study shows that RPCs are likely to be a preferred cell type for retinal transplantation studies, compared with MSCs. However, MSCs may remain an attractive candidate for autologous transplantation.