Centre for Stem Cells and Regenerative Medicine, King's College London, London, UK.
Centre for Craniofacial and Regenerative Biology, King's College London, London, UK.
Nat Mater. 2021 Jan;20(1):108-118. doi: 10.1038/s41563-020-0786-5. Epub 2020 Sep 21.
The maintenance of human skeletal stem cells (hSSCs) and their progeny in bone defects is a major challenge. Here, we report on a transplantable bandage containing a three-dimensional Wnt-induced osteogenic tissue model (WIOTM). This bandage facilitates the long-term viability of hSSCs (8 weeks) and their progeny, and enables bone repair in an in vivo mouse model of critical-sized calvarial defects. The newly forming bone is structurally comparable to mature cortical bone and consists of human and murine cells. Furthermore, we show that the mechanism of WIOTM formation is governed by Wnt-mediated asymmetric cell division of hSSCs. Covalently immobilizing Wnts onto synthetic materials can polarize single dividing hSSCs, orient the spindle and simultaneously generate a Wnt-proximal hSSC and a differentiation-prone Wnt-distal cell. Our results provide insight into the regulation of human osteogenesis and represent a promising approach to deliver human osteogenic constructs that can survive in vivo and contribute to bone repair.
维持人类骨骼干细胞（hSSCs）及其后代在骨缺损中的存在是一个主要挑战。在这里，我们报告了一种可移植的绷带，其中包含一个三维 Wnt 诱导的成骨组织模型（WIOTM）。这种绷带有利于 hSSCs（8 周）及其后代的长期存活，并能在体内关键性颅骨缺损的小鼠模型中促进骨修复。新形成的骨在结构上可与成熟皮质骨相媲美，并且由人源和鼠源细胞组成。此外，我们还表明，WIOTM 形成的机制受 hSSCs 中 Wnt 介导的不对称细胞分裂调控。通过共价固定 Wnts 到合成材料上可以使单个分裂的 hSSC 极化，定向纺锤体并同时产生一个靠近 Wnt 的 hSSC 和一个易分化的远离 Wnt 的细胞。我们的结果提供了对人类成骨作用的调控机制的深入了解，并代表了一种有前途的方法来递送可在体内存活并有助于骨修复的人源成骨构建体。
