Laboratory for Developmental and Stem Cell Biology (DSB), Skeletal Biology and Engineering Research Center (SBE), KU Leuven, Herestraat 49 Box 813, 3000 Leuven, Belgium.
Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, O&N 1 Herestraat 49 bus 813, 3000 Leuven, Belgium.
Philos Trans R Soc Lond B Biol Sci. 2018 Jul 5;373(1750). doi: 10.1098/rstb.2017.0218.
Bone has many functions. It is responsible for protecting the underlying soft organs, it allows locomotion, houses the bone marrow and stores minerals such as calcium and phosphate. Upon damage, bone tissue can efficiently repair itself. However, healing is hampered if the defect exceeds a critical size and/or is in compromised conditions. The isolation or generation of bone-forming progenitors has applicability to skeletal repair and may be used in tissue engineering approaches. Traditionally, bone engineering uses osteochondrogenic stem cells, which are combined with scaffold materials and growth factors. Despite promising preclinical data, limited translation towards the clinic has been observed to date. There may be several reasons for this including the lack of robust cell populations with favourable proliferative and differentiation capacities. However, perhaps the most pertinent reason is the failure to produce an implant that can replicate the developmental programme that is observed during skeletal repair. Pluripotent stem cells (PSCs) can potentially offer a solution for bone tissue engineering by providing unlimited cell sources at various stages of differentiation. In this review, we summarize key embryonic signalling pathways in bone formation coupled with PSC differentiation strategies for the derivation of bone-forming progenitors.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.
骨骼具有多种功能。它负责保护下面的软组织器官，允许运动，容纳骨髓并储存钙和磷酸盐等矿物质。在受损后，骨骼组织可以有效地自我修复。然而，如果缺陷超过临界尺寸和/或处于受损状态，愈合就会受到阻碍。骨形成祖细胞的分离或生成适用于骨骼修复，并可用于组织工程方法。传统上，骨工程使用成软骨细胞性干细胞，这些细胞与支架材料和生长因子结合使用。尽管有有前景的临床前数据，但迄今为止，向临床的转化观察到的效果有限。造成这种情况的原因可能有几个，包括缺乏具有有利增殖和分化能力的稳健细胞群体。然而，也许最相关的原因是未能生产出一种可以复制在骨骼修复过程中观察到的发育程序的植入物。多能干细胞 (PSC) 可以通过在分化的各个阶段提供无限的细胞来源，为骨组织工程提供解决方案。在这篇综述中，我们总结了骨骼形成相关的关键胚胎信号通路以及 PSC 分化策略，以获得成骨祖细胞。本文是主题为“设计人类组织：即将进入你附近的实验室”的特刊的一部分。
