Cell-surface markers identify tissue resident multipotential stem/stromal cell subsets in synovial intimal and sub-intimal compartments with distinct chondrogenic properties

Autor: S. Chubinskaya, Eric Farrell, Kavitha Sivasubramaniyan, Arnavaz A. Hakimiyan, M. Sande, Jan A N Verhaar, G.J.V.M. van Osch, Martin J. Hoogduijn, H.-J. Bühring, Wendy Koevoet
Přispěvatelé: Orthopedics and Sports Medicine, Otorhinolaryngology and Head and Neck Surgery, Oral and Maxillofacial Surgery, Internal Medicine
Rok vydání: 2019
Předmět:
Cartilage
Articular
Male
0301 basic medicine
CD31
Stromal cell
Biomedical Engineering
Context (language use)
Biology
GPI-Linked Proteins
Immunophenotyping
03 medical and health sciences
0302 clinical medicine
Rheumatology
medicine
Humans
Regeneration
Receptors
Growth Factor
Orthopedics and Sports Medicine
CD90
5'-Nucleotidase
Aged
Aged
80 and over
030203 arthritis & rheumatology
Cluster of differentiation
Multipotent Stem Cells
Cartilage
Regeneration (biology)
Synovial Membrane
Cell Differentiation
Middle Aged
Osteoarthritis
Knee
Flow Cytometry
Chondrogenesis
Immunohistochemistry
Cell biology
Platelet Endothelial Cell Adhesion Molecule-1
030104 developmental biology
medicine.anatomical_structure
Case-Control Studies
Leukocyte Common Antigens
Thy-1 Antigens
Female
Receptors
Chemokine
Cell Adhesion Molecules
Zdroj: Osteoarthritis and Cartilage, 27(12), 1831-1840. W.B. Saunders
ISSN: 1063-4584
Popis: Summary Objective Synovium contains multipotent progenitor/stromal cells (MPCs) with potential to participate in cartilage repair. Understanding the identity of these MPCs will allow their therapeutic potential to be fully exploited. Hence this study aimed to identify primary synovial MPCs and characterize them in the context of cartilage regeneration. Methods Primary MPC/MPC-subset specific markers in synovium were identified by FACS analysis of uncultured cells. MPC-subsets from human synovium obtained from patients undergoing total knee arthroplasty were FACS sorted, cultured, immunophenotyped and chondrogenically differentiated. The anatomical localization of MPCs in synovium was examined using immunohistochemistry. Finally, the presence of these MPC subsets in healthy synovium obtained from human organ donors was examined. Results A combination of CD45, CD31, CD73 and CD90 can isolate two distinct MPC-subsets in synovium. These MPC-subsets, freshly isolated from synovium, did not express CD45 or CD31, but expressed CD73. Additionally, a sub-population of CD73+ cells also expressed CD90. CD45−CD31−CD73+CD90− cells were significantly more chondrogenic than CD45−CD31−CD73+CD90+ cells in the presence of TGFβ1. Interestingly, reduced chondrogenic ability of CD73+CD90+ cells could be reversed by the addition of BMP2, showing discrete chondrogenic factor requirements by distinct cell-subsets. In addition, these MPCs had distinct anatomical localization; CD73 was expressed both in intimal and sub-intimal region while CD90 was enriched in the sub-intimal region. We further demonstrated that these subsets are also present in healthy synovium. Conclusions We provide indications that primary MPCs in synovial intima and sub-intima are phenotypically and functionally distinct with different chondrogenic properties.
Databáze: OpenAIRE
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