Single-cell spatiotemporal analysis reveals cell fates and functions of transplanted mesenchymal stromal cells during bone repair

Chengyu Yang; Zeshun Li; Yang Liu; Runpeng Hou; Minmin Lin; Linhao Fu; Decheng Wu; Quanying Liu; Kai Li; Chao Liu

doi:10.1016/j.stemcr.2022.08.008

Single-cell spatiotemporal analysis reveals cell fates and functions of transplanted mesenchymal stromal cells during bone repair

Stem Cell Reports. 2022 Oct 11;17(10):2318-2333. doi: 10.1016/j.stemcr.2022.08.008. Epub 2022 Sep 22.

Authors

Chengyu Yang¹, Zeshun Li¹, Yang Liu¹, Runpeng Hou¹, Minmin Lin¹, Linhao Fu¹, Decheng Wu¹, Quanying Liu¹, Kai Li², Chao Liu³

Affiliations

¹ Department of Biomedical Engineering, College of Engineering, Southern University of Science and Technology, Shenzhen 518055, China; Guangdong Provincial Key Laboratory of Advanced Biomaterials, Southern University of Science and Technology, Shenzhen 518055, China.
² Department of Biomedical Engineering, College of Engineering, Southern University of Science and Technology, Shenzhen 518055, China; Guangdong Provincial Key Laboratory of Advanced Biomaterials, Southern University of Science and Technology, Shenzhen 518055, China. Electronic address: lik@sustech.edu.cn.
³ Department of Biomedical Engineering, College of Engineering, Southern University of Science and Technology, Shenzhen 518055, China; Guangdong Provincial Key Laboratory of Advanced Biomaterials, Southern University of Science and Technology, Shenzhen 518055, China. Electronic address: liuc33@sustech.edu.cn.

Abstract

Mesenchymal stromal cells (MSCs) transplantation could enhance bone repair. However, the cell fate of transplanted MSCs, in terms of their local distribution and spatial associations with other types of cells were poorly understood. Here, we developed a single-cell 3D spatial correlation (sc3DSC) method to track transplanted MSCs based on deep tissue microscopy of fluorescent nanoparticles (fNPs) and immunofluorescence of key proteins. Locally delivered fNP-labeled MSCs enhanced tibial defect repair, increased the number of stem cells and vascular maturity in mice. fNP-MSCs persisted in the defect throughout repair. But only a small portion of transplanted cells underwent osteogenic differentiation (OSX+); a significant portion has maintained their expression of mesenchymal stem cell and skeletal stem cell markers (SCA-1 and PRRX1). Our results contribute to the optimization of MSC-based therapies. The sc3DSC method may be useful in studying cell-based therapies for the regeneration of other tissue types or disease models.

Keywords: blood vessels; bone repair; fluorescent nanoparticle; mesenchymal stromal cells; spatial analysis; stem cell fate.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation / physiology
Mesenchymal Stem Cell Transplantation* / methods
Mesenchymal Stem Cells* / metabolism
Mice
Osteogenesis / physiology
Spatio-Temporal Analysis