Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China; Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
Stem Cell Reports. 2017 Jun 6;8(6):1587-1599. doi: 10.1016/j.stemcr.2017.04.018. Epub 2017 May 18.
Recent studies using defined transcription factors to convert skin fibroblasts into chondrocytes have raised the question of whether osteo-chondroprogenitors expressing SOX9 and RUNX2 could also be generated during the course of the reprogramming process. Here, we demonstrated that doxycycline-inducible expression of reprogramming factors (KLF4 [K] and c-MYC [M]) for 6 days were sufficient to convert murine fibroblasts into SOX9/RUNX2 cellular aggregates and together with SOX9 (S) promoted the conversion efficiency when cultured in a defined stem cell medium, mTeSR. KMS-reprogrammed cells possess gene expression profiles akin to those of native osteo-chondroprogenitors with elevated osteogenic properties and can differentiate into osteoblasts and chondrocytes in vitro, but form bone tissue upon transplantation under the skin and in the fracture site of mouse tibia. Altogether, we provide a reprogramming strategy to enable efficient derivation of osteo-chondrogenic cells that may hold promise for cell replacement therapy not limited to cartilage but also for bone tissues.
最近的研究使用特定的转录因子将皮肤成纤维细胞转化为软骨细胞，这引发了一个问题，即在重编程过程中是否也可以产生表达 SOX9 和 RUNX2 的成骨-软骨前体细胞。在这里，我们证明，6 天的诱导表达重编程因子（KLF4 [K] 和 c-MYC [M]）足以将鼠成纤维细胞转化为 SOX9/RUNX2 细胞聚集体，并且当在定义的干细胞培养基 mTeSR 中培养时，与 SOX9（S）一起促进转化效率。KMS 重编程细胞具有类似于天然成骨-软骨前体细胞的基因表达谱，具有增强的成骨特性，并且可以在体外分化为成骨细胞和软骨细胞，但在皮下和小鼠胫骨骨折部位移植后形成骨组织。总的来说，我们提供了一种重编程策略，可以有效地获得成骨-软骨细胞，这可能为细胞替代疗法提供希望，不仅限于软骨，还包括骨组织。
