Matthews, BryaNaot, DoritCornish, JillianCao, Ye2023-10-172023-10-172023https://hdl.handle.net/2292/66299Tissue-resident stem and progenitor cells are essential for skeletal healing and regeneration throughout life. The periosteum is a major source of adult skeletal stem and progenitor cells (SSPCs) that contribute to fracture healing. Human skeletal stem cells (SSCs) have been identified in embryos, fetuses, or adult bone marrow, but freshly isolated periosteal SSPCs have been less well-characterised. In mice, fracture studies involve the injury response from multiple tissues, but the independent role of periosteum is yet to be fully determined. The overall hypothesis of this thesis is that periosteum is enriched for adult SSPCs compared to other skeletal tissue compartments, and periosteal cells efficiently contribute to local healing. Marker expression was compared in matched skeletal tissues by multi-colour flow cytometry. Sex, age, and osteoarthritis minimally affected human SSPC (hSSPC) phenotype. Periosteum and articular cartilage were enriched for most putative hSSPC markers compared to marrow compartments. In mice, periosteum was also enriched for adult mouse SSPC (mSSPC) markers and populations compared to matched bone marrow and endosteum. After sorting, haematopoietic lineage negative (Lin-) cells from the periosteum showed efficient CFU-F formation compared with Lin- cells from the marrow compartments in both humans and mice. In humans, freshly isolated periosteal CD90+CD34+ cells contained SSPCs with clonal self-renewal and multipotent differentiation capacity in vitro. We designed a murine periosteum scratch injury model which successfully mimicked fracture healing process without breaking the bone. Following local injury, many mSSPC markers and populations rapidly expanded during the early stages of healing. We identified a group of osteoprogenitors labelled by Sca1-CD51+, which expanded and contributed to bone and cartilage upon transplantation. Histologically, these cells mainly resided in the cambium layer of the periosteum and expanded with local injury. CD51+ and CD34+ cells expanded in a model of enhanced healing. In summary, the periosteum is enriched with adult SSPCs and contains unique SSPC populations compared to the bone marrow compartment. We have defined adult SSPCs in the periosteum of humans and mice, although these populations are still heterogeneous. In conclusion, periosteum is a rich source of adult SSPCs, which are primarily quiescent but rapidly respond to injury.Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated.https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htmhttps://creativecommons.org/licenses/by-nc-nd/3.0/nz/Thesis2023-10-16Copyright: The authorhttp://purl.org/eprint/accessRights/OpenAccess