Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jan;20(1):108-118.
doi: 10.1038/s41563-020-0786-5. Epub 2020 Sep 21.

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

Yoshihisa Okuchi #  1 , Joshua Reeves #  1 , Soon Seng Ng #  1 , Daniel H Doro  2 , Sergi Junyent  1 , Karen J Liu  2 , Alicia J El Haj  3 , Shukry J Habib  4
Affiliations

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

Yoshihisa Okuchi et al. Nat Mater. 2021 Jan.

Abstract

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.

PubMed Disclaimer

References

    1. Fernandez de Grado, G. et al. Bone substitutes: a review of their characteristics, clinical use, and perspectives for large bone defects management. J. Tissue Eng. 9, 2041731418776819 (2018).
    1. Bianco, P. & Robey, P. G. Skeletal stem cells. Development 142, 1023–1027 (2015).
    1. Zeitouni, S. et al. Human mesenchymal stem cell-derived matrices for enhanced osteoregeneration. Sci. Transl. Med. 4, 132ra55 (2012).
    1. Tsai, T.-L. & Li, W.-J. Identification of bone marrow-derived soluble factors regulating human mesenchymal stem cells for bone regeneration. Stem Cell Reports 8, 387–400 (2017).
    1. Krause, U. et al. Pharmaceutical modulation of canonical Wnt signaling in multipotent stromal cells for improved osteoinductive therapy. Proc. Natl Acad. Sci. USA 107, 4147–4152 (2010).

Publication types

LinkOut - more resources