Tam Wai Long, O Dorien F, Hiramatsu Kunihiko, Tsumaki Noriyuki, Luyten Frank P, Roberts Scott J
1 Laboratory for Developmental and Stem Cell Biology (DSB) , Skeletal Biology and Engineering Research Center (SBE), KU Leuven, 3000, Leuven, Belgium .
Cell Reprogram. 2014 Feb;16(1):29-39. doi: 10.1089/cell.2013.0060.
Strategies for bone regeneration are undergoing a paradigm shift, moving away from the replication of end-stage bone tissue and instead aiming to recapture the initial events of fracture repair. Although this is known to resemble endochondral bone formation, chondrogenic cell types with favorable proliferative and hypertrophic differentiation properties are lacking. Recent advances in cellular reprogramming have allowed the creation of alternative cell populations with specific properties through the forced expression of transcription factors. Herein, we investigated the in vitro hypertrophic differentiation and in vivo tissue formation capacity of induced chondrogenic cells (iChon cells) obtained through direct reprogramming. In vitro hypertrophic differentiation was detected in iChon cells that contained a doxycycline-inducible expression system for Klf4, cMyc, and Sox9. Furthermore, endochondral bone formation was detected after implantation in nude mice. The bone tissue was derived entirely from host origin, whereas cartilage tissue contained cells from both host and donor. The results obtained highlight the promise of cellular reprogramming for the creation of functional skeletal cells that can be used for novel bone healing strategies.
骨再生策略正在经历范式转变，从复制终末期骨组织转向旨在重现骨折修复的初始事件。尽管已知这类似于软骨内成骨，但缺乏具有良好增殖和肥大分化特性的软骨生成细胞类型。细胞重编程的最新进展使得通过强制表达转录因子来创建具有特定特性的替代细胞群体成为可能。在此，我们研究了通过直接重编程获得的诱导软骨生成细胞（iChon细胞）的体外肥大分化和体内组织形成能力。在含有强力霉素诱导的Klf4、cMyc和Sox9表达系统的iChon细胞中检测到了体外肥大分化。此外，将其植入裸鼠后检测到了软骨内成骨。骨组织完全来源于宿主，而软骨组织包含来自宿主和供体的细胞。所获得的结果突出了细胞重编程在创建可用于新型骨愈合策略的功能性骨骼细胞方面的前景。
