Transdifferentiation of bone marrow stromal cells in hippocampal slice culture model

海马切片培养模型中骨髓基质细胞的转分化

• 批准号: 13671435
• 负责人: KONDOH Takeshi
• 金额: $ 2.18万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671435/
• 关键词: Bone marrow stromal cells; brain grafting; slice culture; retinoic acid; neuronal plasticity; 骨髄細胞; stromal cell; bone marrow; transplantation

New possibilities for repairing the nervous system have arisen since the discovery of stem cells. Recent studies have demonstrated that different types of stem cells can be transplanted successfully in animal models. Adult green mice marrow stromal cells were co-cultured with hippocampal slices. Transdifferentiation to neuron-or glia-like cells occurred exclusively inside slice boundaries appearing at day 3, and then decreasing gradually over 35 days. Neuron-like cells tended to form network-like connections around day 14. The use of retinoic acid greatly enhanced the number of transdifferentiated cells and the best concentration was 10^<-6> M. NeuN Immunohistochemistry was positive in 9.6 ± 1.7% of morphologically transdifferentiated neuron-like cells. GFAP and lba1immunostainings were negative. We concluded that bone marrow stromal cells can be transdifferentiated into neurons, and direct contact with the host brain tissue is essential. Retinoic acid significantly increases the number of transdifferentiated cells as has been reported with other stem cells.

自从干细胞的发现以来，修复神经系统的新可能性出现了。最近的研究表明，不同类型的干细胞可以在动物模型中成功移植。成年绿色小鼠骨髓基质细胞与海马片共培养。向神经元或神经胶质样细胞的转分化仅发生在切片边界内，在第3天出现，然后在35天后逐渐减少。神经元样细胞在第14天左右开始形成网状连接。维甲酸能显著增加神经元样细胞的数量，最佳浓度为10℃~(-6)~(-6)~(-1)M。GFAP和lba1免疫染色均为阴性。我们得出结论，骨髓基质细胞可以转分化为神经元，与宿主脑组织的直接接触是必不可少的。与其他干细胞一样，维甲酸显著增加了转分化细胞的数量。

项目成果

Bhattacharjee AK, Nagashima, t., Kondoh, T., Tamaki, N.: "Quantification of early blood-brain barrier disruption by in sutu brain perfusion technique"Brain Res Protoc.. 8(2). 126-131 (2001)

Bhattacharjee AK、Nagashima, t.、Kondoh, T.、Tamaki, N.：“通过 in sutu 脑灌注技术对早期血脑屏障破坏进行定量”Brain Res Protoc.. 8(2)。

Ohta, K., Nomura, T., Kanno, T., Nagaki, K., Yamamoto, S., Yajima, Y., Kondoh, T., Kohmura, E., Saito, N., Nishizaki, T: "L-trans-PDC enhances Hippocampal neuronal activity by stimulating glial glutamate release Independently of blocking transporters"Bioc

太田 K.、野村 T.、菅野 T.、长崎 K.、山本 S.、矢岛 Y.、近藤 T.、高村 E.、齐藤 N.、西崎 T：“

近藤 威: "ソースとしての骨髄支持細胞の可能性"Clinical Neuroscience. 20. 28-30 (2002)

Takeshi Kondo：“骨髓支持细胞作为来源的可能性”临床神经科学 20. 28-30 (2002)。

Ueyama, T., Ren, Y., Sakai, N., Takahashi, M., Ono, Y., Kondoh, T., Tamaki, N., Saito, N.: "Generation of a constitutively active fragment of PKN in Microglia/macrophages after middle cerebral artery occlusion in rats"J Neurochem.. 79(4). 903-913 (2001)

Ueyama, T.、Ren, Y.、Sakai, N.、Takahashi, M.、Ono, Y.、Kondoh, T.、Tamaki, N.、Saito, N.：“PKN 组成型活性片段的生成

Tada, H., Uchino, M., Nomura, T., Kondoh, T., Saito, N., Yamamura, T., Yajima, Y., Nishizaki, T.: "The anti-dementia drug FK960 stimulates Glial glutamate release via a PKA pathway"Brain Res Mol Brain Res.. 109(1-2). 63-68 (2002)

Tada, H.、Uchino, M.、Nomura, T.、Kondoh, T.、Saito, N.、Yamamura, T.、Yajima, Y.、Nishizaki, T.：“抗痴呆药物 FK960 刺激胶质细胞谷氨酸