Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand.
Department of Surgery, University of Auckland, Auckland, New Zealand.
Bone. 2024 Jan;178:116926. doi: 10.1016/j.bone.2023.116926. Epub 2023 Oct 2.
The periosteum plays a crucial role in bone healing and is an important source of skeletal stem and progenitor cells. Recent studies in mice indicate that diverse populations of skeletal progenitors contribute to growth, homeostasis and healing. Information about the in vivo identity and diversity of skeletal stem and progenitor cells in different compartments of the adult human skeleton is limited. In this study, we compared non-hematopoietic populations in matched tissues from the femoral head and neck of 21 human participants using spectral flow cytometry of freshly isolated cells. High-dimensional clustering analysis indicated significant differences in marker distribution between periosteum, articular cartilage, endosteum and bone marrow populations, and identified populations that were highly enriched or unique to specific tissues. Periosteum-enriched markers included CD90 and CD34. Articular cartilage, which has very poor regenerative potential, showed enrichment of multiple markers, including the PDPNCD73CD164CD146 population previously reported to represent human skeletal stem cells. We further characterized periosteal populations by combining CD90 with other strongly expressed markers. CD90CD34 cells sorted directly from periosteum showed significant colony-forming unit fibroblasts (CFU-F) enrichment, rapid expansion, and consistent multi-lineage differentiation of clonal populations in vitro. In situ, CD90CD34 cells include a perivascular population in the outer layer of the periosteum and non-perivascular cells closer to the bone surface. CD90 cells are also highly enriched for CFU-F in bone marrow and endosteum, but not articular cartilage. In conclusion, our study indicates considerable diversity in the non-hematopoietic cell populations in different tissue compartments within the adult human skeleton, and suggests that periosteal progenitor cells reside within the CD90CD34 population.
骨膜在骨愈合中起着至关重要的作用，是骨骼干/祖细胞的重要来源。最近在小鼠中的研究表明，多种骨骼祖细胞群体有助于生长、稳态和愈合。关于不同部位成年人体骨骼中骨骼干/祖细胞的体内身份和多样性的信息有限。在这项研究中，我们使用新鲜分离细胞的光谱流式细胞术比较了 21 名人类参与者的股骨头和颈匹配组织中的非造血细胞群体。高维聚类分析表明，骨膜、关节软骨、骨内膜和骨髓群体之间的标记物分布存在显著差异，并鉴定了高度富集或特定组织特有的群体。富含骨膜的标记物包括 CD90 和 CD34。具有非常差的再生潜力的关节软骨显示出多种标记物的富集，包括先前报道的代表人类骨骼干/祖细胞的 PDPNCD73CD164CD146 群体。我们通过将 CD90 与其他强烈表达的标记物结合进一步对骨膜群体进行了表征。直接从骨膜中分选的 CD90CD34 细胞表现出明显的集落形成单位成纤维细胞（CFU-F）富集、快速扩增以及体外克隆群体的一致多谱系分化。在原位，CD90CD34 细胞包括骨膜外层的血管周细胞群和靠近骨表面的非血管周细胞群。CD90 细胞在骨髓和骨内膜中也高度富集 CFU-F，但在关节软骨中则不然。总之，我们的研究表明，成年人体骨骼不同组织部位的非造血细胞群体存在相当大的多样性，并表明骨膜祖细胞存在于 CD90CD34 群体中。
