Human Diseased Articular Cartilage Contains a Mesenchymal Stem Cell-Like Population of Chondroprogenitors with Strong Immunomodulatory Responses

Journal of Clinical Medicine

Lee Kaplan¹  Diego Correa¹  Dimitrios Kouroupis¹  Luigi Zagra²  Marco Viganò³  Paola De Luca³  Carlotta Perucca-Orfei³  Alessandra Colombini³  Laura de Girolamo³ 

[1] Department of Orthopedics, UHealth Sports Medicine Institute, University of Miami, Miller School of Medicine, Miami, FL 33146, USA;IRCCS Istituto Ortopedico Galeazzi, Hip Department, Milan 20161, Italy;IRCCS Istituto Ortopedico Galeazzi, Orthopaedic Biotechnology Lab, Milan 20161, Italy;

关键词: cartilage cells;    cartilage-derived stem/progenitor cells;    mesenchymal stem cells;    stemness;    inflammation;    secretome;    immunomodulation;   

DOI  :  10.3390/jcm8040423

来源: DOAJ

【 摘 要 】

Background: osteoarthritic human articular cartilage (AC)-derived cartilage cells (CCs) with same-donor bone marrow (BMSCs) and adipose tissue (ASCs)-derived mesenchymal stem cells were compared, in terms of stemness features, and secretory and immunomodulatory responses to inflammation. Methods: proteoglycan 4 (PRG4) presence was evaluated in AC and CCs. MSCs and CCs (n = 8) were cultured (P1 to P4) and characterized for clonogenicity, nanog homeobox (NANOG), and POU class 5 homeobox 1 (POU5F1) expression, immunotypification, and tri-lineage differentiation. Their basal and interleukin-1β (IL-1β)-stimulated expression of matrix metalloproteases (MMPs), tissue inhibitors (TIMPs), release of growth factors, and cytokines were analyzed, along with the immunomodulatory ability of CCs. Results: PRG4 was mainly expressed in the intact AC surface, whereas shifted to the intermediate zone in damaged cartilage and increased its expression in CCs upon culture. All cells exhibited a similar phenotype and stemness maintenance over passages. CCs showed highest chondrogenic ability, no adipogenic potential, a superior basal secretion of growth factors and cytokines, the latter further increased after inflammatory stimulation, and an immunomodulatory behavior. All stimulated cells shared an increased MMP expression without a corresponding TIMP production. Conclusion: based on the observed features, CCs obtained from pathological joints may constitute a potential tissue-specific therapeutic target or agent to improve damaged cartilage healing, especially damage caused by inflammatory/immune mediated conditions.

【 授权许可】

Unknown