Wnt-modified materials mediate asymmetric stem cell division to direct human osteogenic tissue formation for bone repair

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...

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Bibliographic Details
Published in:Nature materials 2021-01, Vol.20 (1), p.108-118
Main Authors: Okuchi, Yoshihisa, Reeves, Joshua, Ng, Soon Seng, Doro, Daniel H., Junyent, Sergi, Liu, Karen J., El Haj, Alicia J., Habib, Shukry J.
Format: Article
Language:English
Subjects:
631/532/2074
631/61/2035
631/61/2296
639/301/54/2295
Animals
Asymmetry
Biocompatibility
Biomaterials
Biomedical materials
Bone and Bones - cytology
Cell Division
Chemistry and Materials Science
Condensed Matter Physics
Defects
Humans
Materials Science
Mice
Nanotechnology
Optical and Electronic Materials
Osteogenesis
Progeny
Repair
Skull - cytology
Skull - physiology
Stem cells
Stem Cells - cytology
Three dimensional models
Tissue Engineering - methods
Wnt Proteins - metabolism
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Summary: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. 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.
ISSN:1476-1122
1476-4660
DOI:10.1038/s41563-020-0786-5