A single-cell transcriptome of mesenchymal stromal cells to fabricate bioactive hydroxyapatite materials for bone regeneration  

作　　者：Peng Guo Xizhe Liu Penghui Zhang Zhongyuan He Zhen Li Mauro Alini RGeoff Richards Sibylle Grad Martin J.Stoddart Guangqian Zhou Xuenong Zou Danny Chan Wei Tian Dafu Chen Manman Gao Zhiyu Zhou Shaoyu Liu 

机构地区：[1]Innovation Platform of Regeneration and Repair of Spinal Cord and Nerve Injury,Department of Orthopaedic Surgery,The Seventh Affiliated Hospital of Sun Yat-sen University,Shenzhen,China [2]Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology,The First Affiliated Hospital of Sun Yat-sen University,Guangzhou,China [3]AO Research Institute Davos,Davos,Switzerland [4]Shenzhen Key Laboratory of Anti-aging and Regenerative Medicine,Department of Medical Cell Biology and Genetics,Health Sciences Center,Shenzhen University,Shenzhen,China [5]School of Biomedical Sciences,LKS Faculty of Medicine,The University of Hong Kong,Hong Kong SAR,China [6]Laboratory of Bone Tissue Engineering,Beijing Laboratory of Biomedical Materials,Beijing Research Institute of Orthopaedics and Traumatology,Beijing JiShuiTan Hospital,Beijing,China [7]Department of Sport Medicine,Inst Translat Med,The First Affiliated Hospital of Shenzhen University,Shenzhen Second People’s Hospital,Shenzhen,China

出　　处：《Bioactive Materials》2022年第3期281-298,共18页生物活性材料（英文）

基　　金：This study was supported by the National Key R&D Program of China(Grant no.2017YFC1105000);the National Natural Science Foundation of China(Grant no.81772400,31900583,31430030);the Fundamental Research Funds for the Central Universities(Grant no.19ykzd05);the Natural Science Foundation of Guangzhou City(Grant no.201704030082,201807010031);the Foundation of Shenzhen Committee for Science and Technology Innovation(Grant no.JCYJ20190809142211354,GJHZ20180929160004704);the Sanming Project of Medicine in Shenzhen(Grant no.SZSM201911002);and the Beijing Municipal Health Commission(Grant no.BMHC-2021-X,BMHC-2019-9,BMHC-2018-4,PXM2020_026275_000002).Special thanks are extended to Dr.Cheng Ruijuan for technical support.

摘　　要：The osteogenic microenvironment of bone-repairing materials plays a key role in accelerating bone regeneration but remains incompletely defined,which significantly limits the application of such bioactive materials.Here,the transcriptional landscapes of different osteogenic microenvironments,including three-dimensional(3D)hydroxyapatite(HA)scaffolds and osteogenic medium(OM),for mesenchymal stromal cells(MSCs)in vitro were mapped at single-cell resolution.Our findings suggested that an osteogenic process reminiscent of endochondral ossification occurred in HA scaffolds through sequential activation of osteogenic-related signaling pathways,along with inflammation and angiogenesis,but inhibition of adipogenesis and fibrosis.Moreover,we revealed the mechanism during OM-mediated osteogenesis involves the ZBTB16 and WNT signaling pathways.Heterogeneity of MSCs was also demonstrated.In vitro ossification of LRRC75A+MSCs was shown to have better utilization of WNT-related ossification process,and PCDH10+MSCs with superiority in hydroxyapatite-related osteogenic process.These findings provided further understanding of the cellular activity modulated by OM conditions and HA scaffolds,providing new insights for the improvement of osteogenic biomaterials.This atlas provides a blueprint for research on MSC heterogeneity and the osteogenic microenvironment of HA scaffolds and a database reference for the application of bioactive materials for bone regeneration.

关 键 词：INFLAMMATION bioactive finding 

分 类 号：R32[医药卫生—人体解剖和组织胚胎学]