健康和骨关节炎人类软骨中的祖细胞具有广泛的培养扩增能力,同时保留软骨生成特性。
Progenitor Cells in Healthy and Osteoarthritic Human Cartilage Have Extensive Culture Expansion Capacity while Retaining Chondrogenic Properties.
机构信息
Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
出版信息
Cartilage. 2021 Dec;13(2_suppl):129S-142S. doi: 10.1177/19476035211059600. Epub 2021 Nov 20.
OBJECTIVE
Articular cartilage-derived progenitor cells (ACPCs) are a potential new cell source for cartilage repair. This study aims to characterize endogenous ACPCs from healthy and osteoarthritic (OA) cartilage, evaluate their potential for cartilage regeneration, and compare this to cartilage formation by chondrocytes.
DESIGN
ACPCs were isolated from full-thickness healthy and OA human cartilage and separated from the total cell population by clonal growth after differential adhesion to fibronectin. ACPCs were characterized by growth kinetics, multilineage differentiation, and surface marker expression. Chondrogenic redifferentiation of ACPCs was compared with chondrocytes in pellet cultures. Pellets were assessed for cartilage-like matrix production by (immuno)histochemistry, quantitative analyses for glycosaminoglycans and DNA content, and expression of chondrogenic and hypertrophic genes.
RESULTS
Healthy and OA ACPCs were successfully differentiated toward the adipogenic and chondrogenic lineage, but failed to produce calcified matrix when exposed to osteogenic induction media. Both ACPC populations met the criteria for cell surface marker expression of mesenchymal stromal cells (MSCs). Healthy ACPCs cultured in pellets deposited extracellular matrix containing proteoglycans and type II collagen, devoid of type I collagen. Gene expression of hypertrophic marker type X collagen was lower in healthy ACPC pellets compared with OA pellets.
CONCLUSIONS
This study provides further insight into the ACPC population in healthy and OA human articular cartilage. ACPCs show similarities to MSCs, yet do not produce calcified matrix under well-established osteogenic culture conditions. Due to extensive proliferative potential and chondrogenic capacity, ACPCs show potential for cartilage regeneration and possibly for clinical application, as a promising alternative to MSCs or chondrocytes.
目的
关节软骨来源的祖细胞(ACPCs)是软骨修复的一种潜在新细胞来源。本研究旨在对健康和骨关节炎(OA)软骨中的内源性 ACPCs 进行特征描述,评估其软骨再生的潜力,并与软骨细胞的软骨形成进行比较。
设计
通过对纤维连接蛋白的差异黏附,从全厚健康和 OA 人软骨中分离出 ACPCs,并通过克隆生长将其从总细胞群中分离出来。通过生长动力学、多谱系分化和表面标志物表达对 ACPCs 进行特征描述。将 ACPCs 的软骨再分化与微球培养中的软骨细胞进行比较。通过(免疫)组织化学、糖胺聚糖和 DNA 含量的定量分析以及软骨形成和肥大基因的表达,评估微球中软骨样基质的产生。
结果
健康和 OA 的 ACPCs 成功地向成脂和成软骨谱系分化,但在暴露于成骨诱导培养基时未能产生钙化基质。两种 ACPC 群体均符合间充质基质细胞(MSCs)的细胞表面标志物表达标准。在微球中培养的健康 ACPC 沉积含有蛋白聚糖和 II 型胶原的细胞外基质,而缺乏 I 型胶原。与 OA 微球相比,健康 ACPC 微球中肥大标志物 X 型胶原的基因表达较低。
结论
本研究进一步深入了解健康和 OA 人关节软骨中的 ACPC 群体。ACPCs 与 MSCs 相似,但在既定的成骨培养条件下不会产生钙化基质。由于具有广泛的增殖潜力和软骨生成能力,ACPCs 显示出软骨再生的潜力,可能适用于临床应用,是 MSCs 或软骨细胞的有前途的替代物。
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