Intervertebral Disc-Derived Stem Cells Implications for Regenerative Medicine and Neural Repair
Intervertebral Disc-Derived Stem Cells Implications for Regenerative Medicine and Neural Repair
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DOI：
10.1097/brs.0b013e318266a80d
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发表时间：
2013-02-01
期刊：
影响因子：
3
通讯作者：
Fehlings, Michael G.
中科院分区：
文献类型：
--
作者：
Erwin, W. Mark;Islam, Diana;Fehlings, Michael G.
研究设计.椎间盘（IVD）衍生的干/祖细胞的体外和体内评价.确定椎间盘源性干/祖细胞体外成软骨、成脂、成骨和神经分化能力以及体内神经分化能力。组织修复策略需要合适的细胞来源，这些细胞可用于替代死亡或受损的细胞和组织，如干细胞。在这里，我们研究了IVD衍生的干细胞在再生医学方法和神经repair.Methods的潜在用途：非软骨营养不良的犬IVD髓核（NP）细胞被用来产生干/祖细胞（NP祖细胞[NPPC]）和NPPC分化成软骨，脂肪，和神经谱系在体外和体内成神经谱系。比较NPPC与骨髓间充质干细胞在干细胞基因表达方面的差异。检测NP细胞和NPPC中神经嵴标记蛋白0和Brachyury基因的表达。NPPC含有干细胞/祖细胞并表达“干性”基因，例如Sox 2、0 ct 3/4、Nanog、CD 133、巢蛋白和神经细胞粘附分子，但与间充质（基质）干细胞的不同之处在于NPPC对Nanog基因的更高表达。NPPC不表达蛋白0或Brachyury基因，两者均由IVD NP细胞的整体表达。IVD内NPPC的百分比为菌落形成试验得出的总数的1%。NPPC能够在体外分化为沿着软骨形成、脂肪形成和神经形成谱系，在体内能够分化为少突胶质细胞、神经元和星形胶质细胞特异性前体细胞。我们建议，IVD NP代表再生生态位，这表明IVD可以代表神经修复和再生的前体细胞的一个容易获得的来源。
Study Design. An in vitro and in vivo evaluation of intervertebral disc (IVD) derived stem/progenitor cells.Objective. To determine the chondrogenic, adipogenic, osteogenic, and neurogenic differentiation capacity of disc-derived stem/progenitor cells in vitro and neurogenic differentiation in vivo.Summary of Background Data. Tissue repair strategies require a source of appropriate cells that could be used to replace dead or damaged cells and tissues such as stem cells. Here we examined the potential use of IVD-derived stem cells in regenerative medicine approaches and neural repair.Methods: Nonchondrodystrophic canine IVD nucleus pulposus (NP) cells were used to generate stem/progenitor cells (NP progenitor cells [NPPCs]) and the NPPCs were differentiated in vitro into chondrogenic, adipogenic, and neurogenic lineages and in vivo into the neurogenic lineage. NPPCs were compared with bone marrow derived mesenchymal (stromal) stem cells in terms of the expression of stemness genes. The expression of the neural crest marker protein 0 and the Brachyury gene were evaluated in NP cells and NPPCs.Results. NPPCs contain stem/progenitor cells and express "stemness" genes such as Sox2, Oct3/4, Nanog, CD 133, Nestin, and neural cell adhesion molecule but differ from mesenchymal (stromal) stem cells in the higher expression of the Nanog gene by NPPCs. NPPCs do not express protein 0 or the Brachyury gene both of which are expressed by the totality of IVD NP cells. The percentage of NPPCs within the IVD is 1% of the total as derived by colony-forming assay. NPPCs are capable of differentiating along chondrogenic, adipogenic, and neurogenic lineages in vitro and into oligodendrocyte, neuron, and astroglial specific precursor cells in vivo within the compact myelin-deficient shiverer mouse.Conclusion. We propose that the IVD NP represents a regenerative niche suggesting that the IVD could represent a readily accessible source of precursor cells for neural repair and regeneration.