Differentiation of transplanted bone marrow cells in the adult mouse brain
Differentiation of transplanted bone marrow cells in the adult mouse brain
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DOI：
10.1097/00007890-200106270-00006
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发表时间：
2001-06-27
期刊：
影响因子：
6.2
通讯作者：
Shimada, T
中科院分区：
文献类型：
--
作者：
Nakano, K;Migita, M;Shimada, T
背景据报道，骨髓移植可有效预防溶酶体贮积症神经系统恶化的进展，但治疗作用的机制仍有待阐明。干细胞生物学的最新研究表明，骨髓细胞含有非造血干细胞，包括脑前体细胞。为了评估骨髓细胞作为神经系统疾病细胞和基因治疗载体的贡献，我们研究了CSF移植骨髓细胞在成年小鼠脑中的命运。方法。骨髓细胞用含有绿色荧光蛋白基因的逆转录病毒载体进行遗传标记，然后通过全身输注或直接注射移植到受照射的小鼠中。为了鉴定细胞类型，脑切片用抗神经元cen标记物的特异性抗体染色--神经元特异性烯醇化酶（neuronspecific enolase）用于神经元，胶质细胞酸性蛋白（GFAP）用于星形胶质细胞，碳酸酐酶II（carbonic anhydrase II，CAII）用于少突胶质细胞，离子钙结合适配分子1（Iba 1）用于小胶质细胞--然后在共聚焦显微镜下检查。全身灌注后24周，移植细胞表达Iba 1，但不表达其他脑细胞标志物。相反，直接注射12周后，移植细胞用抗GFAP、CAII和Iba 1的抗体染色。骨髓含有当暴露于脑微环境时能够分化成少突胶质细胞、星形胶质细胞和小胶质细胞的细胞。自体骨髓细胞可用作具有神经症状的溶酶体疾病的离体基因治疗的载体。
Background. Bone marrow transplantation is reportedly effective in preventing the progression of neurological deterioration in lysosomal storage disorders, although the mechanism underlying the therapeutic effects remains to be elucidated. Recent research on stem cell biology suggests that bone marrow cells contain nonhematopoietic stem cells, including brain pre-cursor cells. To evaluate the contribution of bone marrow cells as carriers for cell and gene therapy of neurological disorders, we studied the fate csf transplanted bone marrow cells in the adult mouse brain.Methods. Bone marrow cells were genetically marked with a retroviral vector containing the green fluorescence protein gene and then transplanted into irradiated mice by either systemic infusion or direct injection. To identify cell types, brain sections were stained with specific antibodies against neuronal cen markers-neuron specific enolase for neurons, glial fibrillary acidic protein (GFAP) for astrocytes, carbonic anhydrase II (CAII) for oligodendrocytes, and ionized calcium binding adaptor molecule 1 (Iba1) for microglia-and then examined under a confocal microscope.Results. Twenty-four weeks after systemic infusion, transplanted cells expressed Iba1 but none of the other brain cell markers. Conversely, 12 weeks after direct injection, transplanted cells were stained with antibodies against GFAP, CAII, and Iba1.Conclusions. Bone marrow contains cells capable of differentiating into oligodendrocytes, astrocytes, and microglia when exposed to the brain microenvironment. Autologous bone marrow cells may be useful as carriers for ex vivo gene therapy for lysosomal disorders with neurological symptoms.