Division of Orthopaedic Surgery, University of Toronto, Toronto, Canada.
Spine (Phila Pa 1976). 2013 Feb 1;38(3):211-6. doi: 10.1097/BRS.0b013e318266a80d.
An in vitro and in vivo evaluation of intervertebral disc (IVD)-derived stem/progenitor cells.
To determine the chondrogenic, adipogenic, osteogenic, and neurogenic differentiation capacity of disc-derived stem/progenitor cells in vitro and neurogenic differentiation in vivo.
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.
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.
NPPCs contain stem/progenitor cells and express "stemness" genes such as Sox2, Oct3/4, Nanog, CD133, 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.
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.
椎间盘（IVD）衍生的干细胞/祖细胞的体外和体内评估。
确定椎间盘衍生的干细胞/祖细胞在体外的软骨形成、脂肪形成、成骨和神经发生分化能力，以及体内的神经发生分化。
组织修复策略需要合适的细胞来源，这些细胞可以用来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修复中的潜在用途。
非软骨发育不良的犬椎间盘核髓核（NP）细胞被用来产生干细胞/祖细胞（NP 祖细胞[NPPCs]），并将 NPPCs 在体外分化为软骨形成、脂肪形成和神经发生谱系，并在体内分化为神经发生谱系。NPPCs 与骨髓来源的间充质（基质）干细胞在干性基因的表达方面进行了比较。NP 细胞和 NPPCs 中神经嵴标记蛋白 0 和 Brachyury 基因的表达进行了评估。
NPPCs 含有干细胞/祖细胞，并表达“干性”基因，如 Sox2、Oct3/4、Nanog、CD133、Nestin 和神经细胞粘附分子，但与间充质（基质）干细胞不同的是，NPPCs 中 Nanog 基因的表达更高。NPPCs 不表达蛋白 0 或 Brachyury 基因，这两个基因均由 IVD NP 细胞的总体表达。通过集落形成测定，IVD 中 NPPCs 的比例为总细胞的 1%。NPPCs 能够在体外沿着软骨形成、脂肪形成和神经发生谱系分化，并在紧致髓鞘缺失的颤抖鼠体内分化为少突胶质细胞、神经元和星形胶质细胞的特异性前体细胞。
我们提出，IVD NP 代表一个再生龛，这表明 IVD 可能代表一个易于获得的神经修复和再生前体细胞来源。
