Effects of hypoxias and scaffold architecture on rabbit mesenchymal stem cell differentiation towards a nucleus pulposus-like phenotype.
Effects of hypoxias and scaffold architecture on rabbit mesenchymal stem cell differentiation towards a nucleus pulposus-like phenotype.
复制标题
缺氧和支架结构对兔间充质干细胞向髓核样表型分化的影响。
DOI：
10.1016/j.biomaterials.2011.07.049
复制
发表时间：
2011-11
期刊：
影响因子：
14
通讯作者：
Ma, Peter X.
中科院分区：
文献类型：
--
作者：
Feng, Ganjun;Jin, Xiaobing;Hu, Jiang;Ma, Haiyun;Gupte, Melanie J.;Liu, Hao;Ma, Peter X.
关键词：
髓核移植是需要更换退变椎间盘的病人所需要的。骨髓间充质干细胞（MSCs）是髓核再生的潜在自体干细胞来源。然而，利用MSCs构建功能性髓核的关键问题之一是在体外将MSCs分化为髓核表型，并在体内保持其表型稳定性。在本研究中，三维（3D）纳米纤维聚l -丙交酯（PLLA）支架植入多能兔间充质干细胞，并在缺氧室（2% O2）中TGF-β1存在下沿髓核发育路线诱导构建。结果表明，纳米纤维支架能够支持兔骨髓间充质干细胞向髓核样表型分化，其主要表现为几个髓核相关基因（聚集蛋白、II型胶原和Sox-9）的表达上调，细胞外基质（糖胺聚糖（GAG）和II型胶原）的大量沉积，以及髓核特异性标志物缺氧诱导因子(HIF)-1α的持续表达。皮下植入结果证实，植入前的缺氧诱导有助于构建体在体内保持其表型并抵抗钙化。因此，上述数据表明，利用三维纳米纤维支架联合TGF-β1和缺氧诱导再生功能髓核移植物用于椎间盘置换术是有希望的。
Nucleus pulposus grafts are needed for patients requiring replacement of their degenerated intervertebral discs. Bone marrow-derived mesenchymal stem cells (MSCs) are potential autologous stem cell source for the nucleus pulposus regeneration. One of the key issues of constructing functional nucleus pulposus using MSCs, however, is to differentiate MSCs into nucleus pulposus phenotype in vitro and to maintain their phenotypic stability in vivo. In this study, three-dimensional (3D) nanofibrous poly(L-lactide) (PLLA) scaffolds were seeded with multi-potent rabbit MSCs and the constructs were induced along nucleus pulposus development routes in a hypoxia chamber (2% O2) in the presence of TGF-β1. It was found that nanofibrous scaffold could support the differentiation of rabbit MSCs towards a nucleus pulposus-like phenotype in vitro, as evidenced by upregulated expression of a few important nucleus pulposus-associated genes (aggrecan, type II collagen and Sox-9), abundant deposition of extracellular matrix (glycosaminoglycan (GAG) and type II collagen), and the continuous expression of the nucleus pulposus-specific marker, hypoxia-inducible factor (HIF)-1α. The subcutaneous implantation results confirmed that hypoxic induction before implantation could help the constructs to retain their phenotype and resist calcification in vivo. Therefore, the above data showed the promise of using 3D nanofibrous scaffolds in combination with TGF-β1 and hypoxic induction to regenerate functional nucleus pulposus grafts for intervertebral disc replacement.
登录
查看更多内容
人间充质干细胞体内稳定异位软骨形成对体外软骨分化的依赖性
影响因子：
14
作者：
Liu, Kai;Zhou, Guang Dong;Cao, Yilin
通讯作者：
Cao, Yilin
影响因子：
2.3
作者：
Richardson, S. M.;Knowles, R.;Hoyland, J. A.
通讯作者：
Hoyland, J. A.
影响因子：
3
作者：
BUCKWALTER, JA
通讯作者：
BUCKWALTER, JA
影响因子：
14
作者：
Richardson, Stephery M.;Hughes, Nesta;Hoyland, Judith A.
通讯作者：
Hoyland, Judith A.
影响因子：
14
作者：
Joshi, A;Fussell, G;Marcolongo, M
通讯作者：
Marcolongo, M