Human Diseased Articular Cartilage Contains a Mesenchymal Stem Cell-Like Population of Chondroprogenitors with Strong Immunomodulatory Responses
Human Diseased Articular Cartilage Contains a Mesenchymal Stem Cell-Like Population of Chondroprogenitors with Strong Immunomodulatory Responses
复制标题
DOI：
10.3390/jcm8040423
复制
发表时间：
2019-04-01
影响因子：
3.9
通讯作者：
Colombini, Alessandra
中科院分区：
文献类型：
--
作者：
De Luca, Paola;Kouroupis, Dimitrios;Colombini, Alessandra
背景资料：骨关节炎的人关节软骨（AC）衍生的软骨细胞（CC）与相同供体骨髓（BMSC）和脂肪组织（ASC）衍生的间充质干细胞在干性特征以及对炎症的分泌和免疫调节反应方面进行了比较。方法：检测AC和CC中蛋白多糖4（PRG 4）的存在。培养MSC和CC（n = 8）（P1至P4）并表征克隆形成、纳米同源框（NANOG）和POU 5类同源框1（POU 5 F1）表达、免疫分型和三系分化。他们的基础和白细胞介素-1（IL-1）刺激的基质金属蛋白酶（MMPs），组织抑制因子（TIMPs）的表达，生长因子和细胞因子的释放进行了分析，沿着与CC的免疫调节能力。结果如下：PRG 4主要在完整的AC表面表达，而在受损的软骨中转移到中间区，并在培养后增加其在CC中的表达。所有细胞在传代过程中表现出相似的表型和干性维持。CC显示出最高的软骨形成能力，没有成脂潜力，生长因子和细胞因子的上级基础分泌，后者在炎症刺激后进一步增加，以及免疫调节行为。所有刺激的细胞共享增加的MMP表达没有相应的TIMP生产。结论：基于观察到的特征，从病理关节获得的CC可以构成潜在的组织特异性治疗靶点或试剂，以改善受损软骨愈合，特别是由炎症/免疫介导的病症引起的损伤。
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-1 (IL-1)-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.