Engineering physiologically stiff and stratified human cartilage by fusing condensed mesenchymal stem cells
Engineering physiologically stiff and stratified human cartilage by fusing condensed mesenchymal stem cells
复制标题
DOI：
10.1016/j.ymeth.2015.03.016
复制
发表时间：
2015-08-01
期刊：
影响因子：
4.8
通讯作者：
Vunjak-Novakovic, Gordana
中科院分区：
文献类型：
--
作者：
Bhumiratana, Sarindr;Vunjak-Novakovic, Gordana
长期以来，临床尺寸和机械功能的软骨可以由幼年动物软骨细胞改造而成，但不能由临床主要关注的成人间充质干细胞改造而成。为原代软骨细胞开发的方法在用于人类间充质细胞时并不成功。这里讨论的方法旨在采用类似于间充质干细胞在精确定义的时间进行软骨前凝结和融合的机制。通过将间充质体压模到骨基质的表面上来引发软骨的形成。通过图像引导制造骨基质和模具，骨软骨结构被设计成解剖学上精确的形状和尺寸。培养5周后，软骨层呈现生理分层组织形态，表面含有润滑素，体相含有蛋白聚糖和II型胶原，与骨基质界面含有X型胶原，骨相含有I型胶原。由间充质干细胞工程化的人类软骨的杨氏模量和摩擦系数首次达到成人软骨的生理水平。我们认为这种方法可以有效地生成人类骨软骨组织结构。 (C) 2015 Elsevier Inc. 保留所有权利。
For a long time, clinically sized and mechanically functional cartilage could be engineered from young animal chondrocytes, but not from adult human mesenchymal stem cells that are of primary clinical interest. The approaches developed for primary chondrocytes were not successful when used with human mesenchymal cells. The method discussed here was designed to employ a mechanism similar to pre-cartilaginous condensation and fusion of mesenchymal stem cells at a precisely defined time. The formation of cartilage was initiated by press-molding the mesenchymal bodies onto the surface of a bone substrate. By image-guided fabrication of the bone substrate and the molds, the osteochondral constructs were engineered in anatomically precise shapes and sizes. After 5 weeks of cultivation, the cartilage layer assumed physiologically stratified histomorphology, and contained lubricin at the surface, proteoglycans and type II collagen in the bulk phase, collagen type X at the interface with the bone substrate, and collagen type I within the bone phase. For the first time, the Young's modulus and the friction coefficient of human cartilage engineered from mesenchymal stem cells reached physiological levels for adult human cartilage. We propose that this method can be effective for generating human osteochondral tissue constructs. (C) 2015 Elsevier Inc. All rights reserved.