Preparation of Scaffold-Free Tissue-Engineered Constructs Derived from Human Synovial Mesenchymal Stem Cells Under Low Oxygen Tension Enhances Their Chondrogenic Differentiation Capacity
Preparation of Scaffold-Free Tissue-Engineered Constructs Derived from Human Synovial Mesenchymal Stem Cells Under Low Oxygen Tension Enhances Their Chondrogenic Differentiation Capacity
复制标题
低氧张力下人滑膜间充质干细胞衍生的无支架组织工程构建体的制备增强其软骨分化能力
DOI：
10.1089/ten.tea.2015.0458
复制
发表时间：
2016
影响因子：
4.1
通讯作者：
N.
中科院分区：
文献类型：
--
作者：
Yasui;Y.;Chijimatsu;R.;Hart;D.A.;Koizumi;K.;Sugita;N.;Shimomura;K.;Myoui;A..;Yoshikawa;H.;Nakamura;N.
低氧张力（LOT）已被报道可促进干细胞的软骨分化并防止细胞衰老。因此，将LOT条件引入传统的组织工程过程可以进一步提高用于软骨修复的构建体的潜力。本研究的目的是阐明LOT制备对源自滑膜间充质干细胞（MSC）的无支架组织工程构建体（TEC）的软骨分化的可行性，该构建体用于软骨修复的可行性已在先前的临床前和临床研究中得到证实。在LOT条件下培养MSC可防止细胞衰老并促进人滑膜MSC的增殖能力。此外，在LOT条件下（5%O2; LOT-TEC）从人滑膜MSC制备的TEC显示出优于在通常的20%O2（正常氧分压[NOT]; NOT-TEC）下制备的TEC的体外软骨形成分化能力，具有升高的糖胺聚糖产生和升高的软骨形成标记基因表达水平。值得注意的是，LOT-TEC分化成直径约1cm的透明样软骨组织，而没有可检测到的纤维组织的存在，而常规的NOT-TEC分化成透明样和纤维软骨组织的混合物。这是第一次证明，在体外发育的透明样软骨组织的可植入的大小，以软骨损伤，是来自人骨髓间充质干细胞，而不使用外源性支架。氧张力的操纵是一种安全的低成本程序，因此，可能是一个临床相关的选择，以提高TEC介导的软骨修复的质量。
Low oxygen tension (LOT) has been reported to promote chondrogenic differentiation and prevent cellular senescence of stem cells. Therefore, the introduction of LOT conditions into conventional tissue engineering processes could further improve the potential of the constructs generated for cartilage repair. The purpose of this study was to elucidate the feasibility of LOT preparation on the chondrogenic differentiation of a scaffold-free tissue-engineered construct (TEC) derived from synovial mesenchymal stem cells (MSCs), construct whose feasibility for cartilage repair has been demonstrated in previous preclinical and clinical studies. Culture of MSCs under LOT conditions prevented cellular senescence and promoted the proliferative capacity of human synovial MSCs. In addition, TEC prepared from human synovial MSCs under LOT conditions (5% O2; LOT-TEC) showed superiorin vitrochondrogenic differentiation capacity compared to that prepared under the usual 20% O2(normal oxygen tension [NOT]; NOT-TEC), with elevated glycosaminoglycan production and elevated levels of chondrogenic marker gene expression. Notably, LOT-TEC differentiated into a hyaline-like cartilaginous tissue of approximately 1 cm in diameter without the detectable presence of fibrous tissue, while conventional NOT-TEC differentiated into a mixture of hyaline-like and fibrocartilaginous tissues. This is the first demonstration ofin vitrodevelopment of a hyaline-like cartilaginous tissue of an implantable size to chondral lesion that was derived from human MSCs without the use of an exogenous scaffold. The manipulation of oxygen tension is a safe procedure with low cost and, thus, may be a clinically relevant option to improve the quality of TEC-mediated cartilage repair.