De Luca Paola, Kouroupis Dimitrios, Viganò Marco, Perucca-Orfei Carlotta, Kaplan Lee, Zagra Luigi, de Girolamo Laura, Correa Diego, Colombini Alessandra
IRCCS Istituto Ortopedico Galeazzi, Orthopaedic Biotechnology Lab, Milan 20161, Italy.
Department of Orthopedics, UHealth Sports Medicine Institute, University of Miami, Miller School of Medicine, Miami, FL 33146, USA.
J Clin Med. 2019 Mar 28;8(4):423. doi: 10.3390/jcm8040423.
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.
proteoglycan 4 (PRG4) presence was evaluated in AC and CCs. MSCs and CCs ( = 8) were cultured (P1 to P4) and characterized for clonogenicity, nanog homeobox (), and POU class 5 homeobox 1 () 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.
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.
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.
比较了来自骨关节炎患者关节软骨（AC）的软骨细胞（CCs）与来自同一供体骨髓（BMSCs）和脂肪组织（ASCs）的间充质干细胞，观察其干性特征以及对炎症的分泌和免疫调节反应。
评估了AC和CCs中蛋白聚糖4（PRG4）的存在情况。培养了间充质干细胞和CCs（n = 8）（传代1至4次），并对其克隆形成能力、纳米盒基因（nanog）和POU5类同源框1基因（OCT4）的表达、免疫分型以及三系分化进行了鉴定。分析了它们在基础状态下和白细胞介素-1β（IL-1β）刺激下基质金属蛋白酶（MMPs）、组织抑制剂（TIMPs）的表达、生长因子和细胞因子的释放情况，以及CCs的免疫调节能力。
PRG4主要表达于完整的AC表面，而在受损软骨中转移至中间区域，并在培养后CCs中表达增加。所有细胞在传代过程中均表现出相似的表型和干性维持。CCs表现出最高的软骨形成能力，无脂肪形成潜力，生长因子和细胞因子的基础分泌水平较高，炎症刺激后进一步增加，并且具有免疫调节行为。所有受刺激的细胞MMP表达均增加，但未产生相应的TIMP。
基于观察到的特征，从病理关节获得的CCs可能构成潜在的组织特异性治疗靶点或药物，以改善受损软骨的愈合，特别是由炎症/免疫介导的疾病所导致的损伤。
