Periosteal skeletal stem cells can migrate into the bone marrow and support hematopoiesis after injury

Skeletal stem cells (SSCs) have been isolated from various tissues, including periosteum and bone marrow, where they exhibit key functions in bone biology and hematopoiesis, respectively. The role of periosteal SSCs (P-SSCs) in bone regeneration and healing has been extensively studied, but their ability to contribute to the bone marrow stroma is still under debate. In the present study, we characterized a mouse whole bone transplantation model that mimics the initial bone marrow necrosis and fatty infiltration seen after injury. Using this model and a lineage tracing approach, we observed the migration of P-SSCs into the bone marrow after transplantation. Once in the bone marrow, P-SSCs are phenotypically and functionally reprogrammed into bone marrow mesenchymal stem cells (BM-MSCs) that express high levels of hematopoietic stem cell niche factors such as Cxcl12 and Kitl. In addition, using ex vivo and in vivo approaches, we found that P-SSCs are more resistant to acute stress than BM-MSCs. These results highlight the plasticity of P-SSCs and their potential role in bone marrow regeneration after bone marrow injury.