Bone marrow CD73 mesenchymal stem cells display increased stemness and promote fracture healing .

Mesenchymal stem cells (MSCs) are multipotent and considered to be of great potential for regenerative medicine. We could show recently (Breitbach, Kimura et al. 2018) that a subpopulation of MSCs as well as sinusoidal endothelial cells (sECs) in the bone marrow (BM) of CD73-EGFP reporter mice could be labeled . We took advantage of this model to explore the plasticity and osteogenic potential of CD73-EGFP MSCs and their role in the regenerative response upon bone lesion . Herein we show that isolated CD73-EGFP MSCs displayed more pronounced stemness and stronger differentiation capacity into the osteogenic lineage compared to CD73-EGFP MSCs. In a bone fracture model, endogenous BM-resident CD73-EGFP MSCs were found to migrate to the fracture site and differentiate into cartilage and bone cells. Our analysis also showed that CD73-EGFP sECs contributed to the neovascularization of the fracture site. In addition, grafting of CD73-EGFP MSCs into acute bone lesions revealed their capacity to differentiate into chondrocytes and osteocytes and their contribution to callus formation in the regeneration process of fracture healing. Thus, CD73 MSCs display enhanced stemness and osteogenic differentiation potential and illustrating a prominent role of the CD73 MSC subpopulation to promote fracture repair.