CHONDROGENIC DIFFERENTIATION OF HUMAN BONE MARROW-DERIVED MESENCHYMAL STEM CELLS IN A SIMULATED OSTEOCHONDRAL ENVIRONMENT IS HYDROGEL DEPENDENT
CHONDROGENIC DIFFERENTIATION OF HUMAN BONE MARROW-DERIVED MESENCHYMAL STEM CELLS IN A SIMULATED OSTEOCHONDRAL ENVIRONMENT IS HYDROGEL DEPENDENT
复制标题
DOI：
10.22203/ecm.v027a09
复制
发表时间：
2014-01-01
影响因子：
3.1
通讯作者：
van Osch, Gerjo J. V. M.
中科院分区：
文献类型：
--
作者：
de Vries-van Melle, Marloes L.;Tihaya, Maria S.;van Osch, Gerjo J. V. M.
水凝胶为软骨再生策略提供了有趣的特征，例如可注射性和原位凝胶化的选项，从而达到最佳的填充效果。我们的目的是研究不同的水凝胶支持人骨髓间充质干细胞(HBMSCs)软骨形成的能力。将hBMSCs包裹于海藻酸盐、海藻酸盐与透明质酸复合(藻酸盐/HA)、纤维蛋白或热敏性HA与聚N-异丙基丙烯酰胺侧链(HA-PNIPAM)。在hBMSC-海藻酸盐和hBMSC-纤维蛋白构建物中，糖胺多糖的产生和软骨相关基因的表达显著高于其他构建物。添加海藻酸盐和透明质酸无益。将hBMSC-藻酸盐、hBMSC-纤维蛋白和hBMSC-HA-PNIPAM构建物植入模拟骨软骨组织缺损处，体外培养28d，将含有hBMSC-藻酸盐和hBMSC-纤维蛋白的组织块植入裸鼠皮下12周。培养28d后，hBMSC-藻酸盐构建物的软骨相关基因表达显著高于hBMSC-藻酸盐构建物，12周后体内藏红素-O阳性修复组织明显多于hBMSC-纤维蛋白构建物。虽然hBMSC-水凝胶构建物的初步实验结果与hBMSC-藻酸盐、hBMSC-纤维蛋白和hBMSC-HA-PNIPAM构建物相似，但在体外和体内骨软骨活组织模型中的培养显示出差异，表明hBMSCs在骨软骨环境中的软骨形成是水凝胶依赖的。
Hydrogels pose interesting features for cartilage regeneration strategies, such as the option for injectability and in situ gelation resulting in optimal filling of defects. We aimed to study different hydrogels for their capability to support chondrogenesis of human bone marrow-derived mesenchymal stem cells (hBMSCs). hBMSCs were encapsulated in alginate, alginate with hyaluronic acid (alginate/HA), fibrin or thermoresponsive HA grafted with poly(N-isopropyl acrylamide) side-chains (HA-pNIPAM). Glycosaminoglycan production and cartilage-related gene expression were significantly higher in hBMSC-alginate and hBMSC-fibrin constructs than in the other constructs. Supplementation of alginate with HA was not beneficial. hBMSC-alginate, hBMSC-fibrin and hBMSC-HA-pNIPAM constructs were placed in simulated defects in osteochondral biopsies and cultured in vitro for 28 d. Biopsies containing hBMSC-alginate and hBMSC-fibrin were implanted subcutaneously in nude mice for 12 weeks. hBMSC-alginate constructs had significantly higher cartilage-related gene expression after 28 d of culture as well as significantly more safranin-O positive repair tissue after 12 weeks in vivo than hBMSC-fibrin constructs. Although initial experiments with hBMSC-hydrogel constructs suggested comparable results of hBMSC-alginate, hBMSC-fibrin and hBMSC-HA-pNIPAM constructs, culture in the osteochondral biopsy model in vitro as well as in vivo revealed differences, suggests that chondrogenesis of hBMSCs in an osteochondral environment is hydrogel-dependent.