Mesenchymal Stem Cells Promote Oligodendroglial Differentiation in Hippocampal Slice Cultures

Mesenchymal Stem Cells Promote Oligodendroglial Differentiation in Hippocampal Slice Cultures
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DOI:
10.1159/000233256
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发表时间:
2009-01-01
影响因子:
--
通讯作者:
Aigner, Ludwig
Aigner, Ludwig
中科院分区:
医学1区
文献类型:
--
作者:
Rivera, Francisco J.;Siebzehnrubl, Florian A.;Aigner, Ludwig

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我们以前已经表明,可溶性因子来源于间充质干细胞(MSC)诱导少突分化的命运和分化的成年大鼠神经祖细胞(NPC)在体外。在这里,我们研究了这种促少突胶质细胞生成的作用是否在细胞移植到大鼠海马切片培养物(CNS器官型环境)后保持。我们首先测试了通过MSC衍生的条件培养基在体外预分化的NPC在移植后是否会产生少突胶质细胞。这种方法导致移植的NPC的损失,表明少突胶质细胞预分化的细胞不能整合在组织中,因此不能存活移植。然而,当NPCs与MSC一起原位移植到海马脑片培养物中时,移植的NPCs存活,并且其中大多数分化为少突胶质细胞。与NPC/MSC共移植的情况下普遍的少突胶质细胞分化相反,在没有MSC的情况下移植的幼稚NPC主要分化为星形胶质细胞。总之,只有在共移植到海马切片培养物中后,MSC的促少突分化活性才得以维持。因此,在其他星形环境中,MSC为移植的NPC建立了少突胶质细胞生成的生态位,因此,MSC与NPC的共移植可能提供一种有吸引力的方法来使患病CNS的各个区域重新髓鞘化。版权所有(C)2009 S. Karger AG,巴塞尔
We have previously shown that soluble factors derived from mesenchymal stem cells (MSCs) induce oligodendrogenic fate and differentiation in adult rat neural progenitors (NPCs) in vitro. Here, we investigated if this pro-oligodendrogenic effect is maintained after cells have been transplanted onto rat hippocampal slice cultures, a CNS-organotypic environment. We first tested whether NPCs, that were pre-differentiated in vitro by MSC-derived conditioned medium, would generate oligodendrocytes after transplantation. This approach resulted in the loss of grafted NPCs, suggesting that oligodendroglial pre-differentiated cells could not integrate in the tissue and therefore did not survive grafting. However, when NPCs together with MSCs were transplanted in situ into hippocampal slice cultures, the grafted NPCs survived and the majority of them differentiated into oligodendrocytes. In contrast to the prevalent oligodendroglial differentiation in case of the NPC/MSC co-transplantation, naive NPCs transplanted in the absence of MSCs differentiated predominantly into astrocytes. In summary, the pro-oligodendrogenic activity of MSCs was maintained only after co-transplantation into hippocampal slice cultures. Therefore, in the otherwise astrogenic milieu, MSCs established an oligodendrogenic niche for transplanted NPCs, and thus, co-transplantation of MSCs with NPCs might provide an attractive approach to re-myelinate the various regions of the diseased CNS. Copyright (C) 2009 S. Karger AG, Basel