Characterization of adult human skeletal cells in different tissues reveals a CD90+CD34+ periosteal stem/progenitor population

Ye Cao; Scott M Bolam; Anna L Boss; Helen C Murray; Jacob T Munro; Raewyn C Poulsen; Nicola Dalbeth; Anna E S Brooks; Brya G Matthews

doi:10.1016/j.bone.2023.116926

Characterization of adult human skeletal cells in different tissues reveals a CD90⁺CD34⁺ periosteal stem/progenitor population

Bone. 2024 Jan:178:116926. doi: 10.1016/j.bone.2023.116926. Epub 2023 Oct 2.

Authors

Ye Cao¹, Scott M Bolam², Anna L Boss³, Helen C Murray⁴, Jacob T Munro², Raewyn C Poulsen⁵, Nicola Dalbeth⁶, Anna E S Brooks⁷, Brya G Matthews⁸

Affiliations

¹ Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand.
² Department of Surgery, University of Auckland, Auckland, New Zealand.
³ Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand.
⁴ Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New Zealand.
⁵ Department of Pharmacology, University of Auckland, Auckland, New Zealand.
⁶ Department of Medicine, University of Auckland, Auckland, New Zealand.
⁷ School of Biological Sciences, University of Auckland, Auckland, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand.
⁸ Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand. Electronic address: brya.matthews@auckland.ac.nz.

PMID: 37793499
DOI: 10.1016/j.bone.2023.116926

Abstract

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 PDPN⁺CD73⁺CD164⁺CD146^- population previously reported to represent human skeletal stem cells. We further characterized periosteal populations by combining CD90 with other strongly expressed markers. CD90⁺CD34⁺ 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, CD90⁺CD34⁺ 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 CD90⁺CD34⁺ population.

Keywords: Mesenchymal stem cells; Periosteum; Progenitor; Prospective isolation; Skeletal stem cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Animals
Antigens, CD34
Biomarkers
Cell Adhesion Molecules*
Cell Differentiation
Humans
Mice
Periosteum
Stem Cells*

Substances

Antigens, CD34
Biomarkers
Cell Adhesion Molecules