Microscopy image of periosteal skeletal stem cells (green) that have migrated into the bone marrow and adopted characteristics of bone marrow mesenchymal stromal cells, enwrapping the blood vessels (red) inside the bone marrow. Image credit: Marchand et al., 2025 (CC BY 4.0)
Bone marrow is the soft tissue inside the bones in our bodies. It is the main production facility for new blood cells and makes billions of blood cells daily. However, like any other tissue or organ, the bone marrow can be damaged, for example, by radiation, chemotherapy drugs, or physical injuries like broken bones.
Bone marrow mesenchymal stromal cells or BM-MSCs are a key component of the bone marrow and are responsible for regulating self-renewal, and for proliferation and differentiation of a group of blood-cell producing stem cells called hematopoietic stem cells or HSCs.
A type of skeletal stem cell, the periosteal skeletal stem cells or P-SSCs, are located in a part of the bone called the periosteum, a thin tissue surrounding long bones. These cells are known to help bones regenerate and heal following a fracture. They are thought to share functional similarities with BM-MSCs. However, it is unclear if P-SSCs also support the recovery of blood cell production after damage to the bone marrow.
To find out more, Marchand, Akkinola et al. used bone tissue derived from genetically engineered mice whose P-SSCs produced a fluorescent tag. Transplanting this bone tissue into otherwise healthy mice mimicked the changes usually seen in the bone marrow after an injury. Microscopy imaging of the transplanted bone at different stages revealed that P-SSCs migrated into the bone marrow after the transplantation injury.
Once in the bone marrow, the P-SSCs developed BM-MSC-like characteristics, producing proteins known to support HSPCs. In other words, P-SSCs effectively transformed into new BM-MSCs, to the extent that the transplanted bone marrow could begin producing blood cells again. Further genetic analysis of P-SSCs and BM-MSCs showed that genes involved in stress resistance were more active in the P-SSCs. This suggests that P-SSCs are better at responding to stress, which may be helpful immediately after an injury.
Marchand, Akkinola et al. have developed a new model to study how the bone marrow repairs itself after it is damaged. These findings may help contribute to a more detailed understanding of the mechanisms behind bone marrow regeneration, as well as treatments to improve recovery following injury.
