He Jing, Guo Jianglong, Jiang Bo, Yao Ruijuan, Wu Yao, Wu Fang
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, P.R. China.
Regen Biomater. 2017 Oct;4(5):269-279. doi: 10.1093/rb/rbx008. Epub 2017 Apr 11.
While both induction culture media and matrix have been reported to regulate the stem cell fate, little is known about which factor plays a more decisive role in directing the MSC differentiation lineage as well as the underlying mechanisms. To this aim, we seeded MSCs on HA-collagen and HA-synthetic hydrogel matrixes, which had demonstrated highly different potentials toward osteoblastic and chondrocytic differentiation lineages, respectively, and cultured them with osteogenic, chondrogenic and normal culture media, respectively. A systematic comparison has been carried out on the effects of induction media and matrix on MSC adhesion, cytoskeleton organization, proliferation, and in particular differentiation into the osteoblastic and chondrocytic lineages. The results demonstrated that the matrix selection had a much more profound effect on directing the differentiation lineage than the induction media did. The strong modulation effect on the transcription activities might be the critical factor contributing to the above observations in our study, where canonical Wnt-β-Catenin signal pathway was directly involved in the matrix-driven osteoblastic differentiation. Such findings not only provide a critical insight on natural cellular events leading to the osteoblastic and chondrocytic differentiations, but also have important implications in biomaterial design for tissue engineering applications.
虽然已有报道称诱导培养基和基质都能调节干细胞命运，但对于在引导间充质干细胞分化谱系方面哪个因素起更决定性作用以及潜在机制，人们了解甚少。为此，我们将间充质干细胞接种在分别对成骨和成软骨分化谱系显示出高度不同潜能的HA-胶原蛋白和HA-合成水凝胶基质上，并分别用成骨、成软骨和正常培养基进行培养。我们对诱导培养基和基质对间充质干细胞黏附、细胞骨架组织、增殖，特别是向成骨和成软骨谱系分化的影响进行了系统比较。结果表明，与诱导培养基相比，基质选择对引导分化谱系的影响更为深远。对转录活性的强烈调节作用可能是导致我们研究中上述观察结果的关键因素，其中经典的Wnt-β-连环蛋白信号通路直接参与了基质驱动的成骨分化。这些发现不仅为导致成骨和成软骨分化的自然细胞事件提供了关键见解，也对组织工程应用中的生物材料设计具有重要意义。
