Jawbone Mesenchymal Stromal Cells Attenuate Acute Inflammation via CXCL12-Mediated Hematopoietic Niche Reinforcement

Xinyu WangQianye ChenJiping SunZijian ZhangTingwei LuXiangru HuangSiyuan SunYuanqi LiuHouwen PanQinggang Dai^*Lei Shen^*Lingyong Jiang^*

• Shanghai Jiao Tong University, Shanghai, China

Background: The bone marrow microenvironment, comprising various cell types and molecular signals, finely orchestrates the selfrenewal and lineage commitment of hematopoietic stem cells (HSCs). Although most investigations have centered on mesenchymal stem cells (MSCs) from long bones, the distinct properties and immunoregulatory functions of craniofacial bone marrow derived MSCs remain largely unexplored. Notably, jawbone MSCs not only exhibit a robust capacity for promoting hematopoietic regeneration but also offer therapeutic potential in infectious diseases. Results: Singlecell sequencing revealed a robust interaction between jawbone MSCs and HSCs. Tissue immunofluorescence demonstrated that in the mouse jawbone, MSCs and HSCs were located in close spatial proximity. In vitro osteogenic and adipogenic induction experiments showed that jawbone MSCs possess considerable multilineage differentiation potential. Co-culture assays further indicated that jawbone MSCs induce HSCs to differentiate into various immune cell types, particularly promoting B cell generation. RT-qPCR and immunofluorescence assays confirmed that pivotal transcription factors, such as PAX5, were activated in B cells. In an in vivo infection model, jawbone MSCs exhibited significant antiinfective capabilities, effectively reducing mortality and systemic inflammation in infected mice. A deeper analysis of the single-cell sequencing data revealed that jawbone MSCs mainly facilitate hematopoiesis by secreting CXCL12. Conclusion: Through single-cell sequencing, in vitro multilineage induction, co-culture systems, and a mouse model of LPSinduced acute infection, this study systematically elucidates the close interplay between jawbone MSCs and HSCs, as well as their pivotal roles in immune modulation and antiinfective responses. The findings demonstrate that jawbone MSCs not only exhibit robust multilineage differentiation potential but also secrete CXCL12 and activate key B cell transcription factors (such as PAX5). This process significantly promotes HSC differentiation into B cells, improves survival rates in infected mice, and attenuates systemic inflammation. These results establish a strong foundation for further investigation into the applications of jawbone MSCs in immune regulation and disease therapy.