Human mesenchymal stem cell differentiation to NP-like cells in chitosan-glycerophosphate hydrogels
Human mesenchymal stem cell differentiation to NP-like cells in chitosan-glycerophosphate hydrogels
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DOI：
10.1016/j.biomaterials.2007.09.018
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发表时间：
2008-01-01
期刊：
影响因子：
14
通讯作者：
Hoyland, Judith A.
中科院分区：
文献类型：
--
作者：
Richardson, Stephery M.;Hughes, Nesta;Hoyland, Judith A.
椎间盘退变是引起腰痛的主要原因之一。由于目前的临床治疗旨在恢复生物力学功能和提供症状缓解，关注生物修复方法的兴趣增加了。已经提出了几种使用不同细胞类型和水凝胶/支架的组织工程方法。由于退化细胞不适合用于组织工程，人们的注意力集中在间充质干细胞（MSCs）的使用上。此外，虽然刚性支架已被证明可以使间充质干细胞分化为IVD的软骨细胞样细胞，但由于水凝胶可以实现微创植入而不会对IVD造成广泛损伤，因此对其的研究越来越多。在这里，我们研究了温度敏感的水凝胶壳聚糖-甘油磷酸酯（C/Gp），用人间充质干细胞播种，在标准培养基中培养4周。我们分析了MSCs的基因和蛋白表达谱，并将其与C/Gp培养的髓核细胞和关节软骨细胞进行了比较。软骨细胞标记基因的基因表达分析表明MSCs分化为一种与关节软骨细胞和NP细胞相似的表型。常规PCR显示成骨标记基因和增生性标记基因X型胶原缺乏表达。MSCs分泌蛋白聚糖和胶原的比例也与NP细胞比关节软骨细胞更接近。因此，这些结果表明msc种子C/Gp凝胶可用于临床变性人IVD的再生。(c) 2007 Elsevier Ltd.版权所有。
Intervertebral disc (IVD) degeneration is one of the major causes of low back pain. As current clinical treatments are aimed at restoring biomechanical function and providing symptomatic relief, interest in methods focused on biological repair has increased. Several tissue engineering approaches using different cell types and hydrogels/scaffolds have been proposed. Owing to the unsuitable nature of degenerate cells for tissue engineering attention has focused on the use of mesenchymal stem cells (MSCs). Additionally, while rigid scaffolds have been demonstrated to allow MSC differentiation to the chondrocyte-like cells of the IVD, hydrogels are being increasingly studied as they allow minimally invasive implantation without extensive damage to the IVD. Here, we have studied the temperature-sensitive hydrogel chitosan-glycerophosphate (C/Gp), seeded with human MSCs and cultured for 4 weeks in standard medium. We have analysed the gene and protein expression profile of the MSCs and compared it to that of both nucleus pulposus (NP) cells and articular chondrocytes cultured in C/Gp. Gene expression analysis for chondrocytic-cell marker genes demonstrated differentiation of MSCs to a phenotype which showed similarities to both articular chondrocytes and NP cells. Conventional PCR demonstrated a lack of expression of osteogenic marker genes and the hypertrophic marker gene type X collagen. MSCs also secreted both proteoglycans and collagens in a ratio, which more closely resembled that of NP cells than articular chondrocytes. These results therefore suggest that MSC-seeded C/Gp gels could be used clinically for the regeneration of the degenerate human IVD. (c) 2007 Elsevier Ltd. All rights reserved.