Molecular pathways involved in neural in vitro differentiation of marrow stromal stem cells
Molecular pathways involved in neural in vitro differentiation of marrow stromal stem cells
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DOI：
10.1002/jcb.20315
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发表时间：
2005-03-01
影响因子：
4
通讯作者：
Galderisi, U
中科院分区：
文献类型：
--
作者：
Jori, FP;Napolitano, MA;Galderisi, U
近年来，一些报道声称证明了转分化，即干细胞来源于给定的组织，并在移植或体外处理后分化成不同组织的表型特征。例如，存在于骨髓中的间充质干细胞，也称为骨髓基质干细胞（MSC），已经被诱导分化成神经元。我们决定通过分子和形态学的后续研究来更深入地研究这种现象。我们分析了目前诱导触发神经元样的承诺和MSC成熟的生化途径。我们的研究表明：W的cAMP的增加，诱导分化的MSC，激活经典的PKA途径，而不是通过交换蛋白直接激活的cAMP（EPAC），一个鸟嘌呤核苷酸交换因子的小GTdR Rap 1和Rap 2;（ii）MEK-ERK信号可能有助于神经的承诺和分化;（iii）CaM KII活性似乎是神经元分化。相反，它的抑制可能有助于拯救分化细胞免于死亡。我们的研究还表明，目前使用的体外分化方案虽然允许神经分化的早期步骤发生，但不能进一步维持这一过程。(C)2004 Wiley-Liss，Inc.
In recent years several reports have claimed to demonstrate trans-differentiation, namely that stern cells have been derived from a given tissue and have differentiated into phenotypes characteristic of different tissues following transplantation or in vitro treatment. For example, the mesenchymal stem cells, also referred to as marrow stromal stem cells (MSCs), present in bone marrow, have been induced to differentiate into neurons. We decided to investigate this phenomenon more in depth by a molecular and morphological follow-up. We analyzed the biochemical pathways that are currently induced to trigger neuron-like commitment and maturation of MSCs. Our studies suggest that: W the increase in cAMP, induced to differentiate MSCs, activates the classical PKA pathway and not through the exchange protein directly activated by cAMP (EPAC), a guanine nucleotide exchange factor for the small GTPase Rap1 and Rap2; (ii) MEK-ERK signaling could contribute to neural commitment and differentiation; (iii) CaM KII activity seems dispensable for neuron differentiation. On the contrary, its inhibition could contribute to rescuing differentiating cells from death. Our research also indicates that the Currently used in vitro differentiation protocols, while they allow the early steps of neural differentiation to take place, are not able to further sustain this process. (C) 2004 Wiley-Liss, Inc.