Wnt-modified materials mediate asymmetric stem cell division to direct human osteogenic tissue formation for bone repair
Wnt-modified materials mediate asymmetric stem cell division to direct human osteogenic tissue formation for bone repair
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DOI：
10.1038/s41563-020-0786-5
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发表时间：
2020-09-21
期刊：
影响因子：
41.2
通讯作者：
Habib, Shukry J.
中科院分区：
文献类型：
--
作者：
Okuchi, Yoshihisa;Reeves, Joshua;Habib, Shukry J.
Wnt 3a蛋白被固定在生物相容性绷带上，可诱导人骨骼干细胞定向不对称分裂，并在体内促进骨组织修复，如何维持人骨骼干细胞及其后代在骨缺损中的存活是一个重大挑战。在这里，我们报告了一个可移植的绷带包含一个三维Wnt诱导的成骨组织模型（WIOTM）。该绷带促进hSSC（8周）及其后代的长期存活力，并且能够在临界尺寸的颅骨缺损的体内小鼠模型中进行骨修复。新形成的骨在结构上与成熟的皮质骨相当，由人和鼠细胞组成。此外，我们表明WIOTM形成的机制是由Wnt介导的hSSC的不对称细胞分裂控制的。将Wnt共价固定在合成材料上可以使单个分裂的hSSC分裂，定向纺锤体并同时产生Wnt近端hSSC和倾向于分化的Wnt远端细胞。我们的研究结果提供了对人类成骨调控的深入了解，并代表了一种有前途的方法来提供可以在体内存活并有助于骨修复的人类成骨结构。
Wnt3a protein has been immobilized on a biocompatible bandage and is now shown to induce oriented asymmetric cell division of human skeletal stem cells and can also promote bone tissue repair in vivo.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.