Department of Trauma, Hand, Plastic and Reconstructive Surgery, University of Würzburg, Oberdürrbacher Str. 6, 97080 Würzburg, Germany.
Department of Orthopedics, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.
Int J Mol Sci. 2020 Sep 25;21(19):7071. doi: 10.3390/ijms21197071.
Identification of articular cartilage progenitor cells (ACPCs) has opened up new opportunities for cartilage repair. These cells may be used as alternatives for or in combination with mesenchymal stromal cells (MSCs) in cartilage engineering. However, their potential needs to be further investigated, since only a few studies have compared ACPCs and MSCs when cultured in hydrogels. Therefore, in this study, we compared chondrogenic differentiation of equine ACPCs and MSCs in agarose constructs as monocultures and as zonally layered co-cultures under both normoxic and hypoxic conditions. ACPCs and MSCs exhibited distinctly differential production of the cartilaginous extracellular matrix (ECM). For ACPC constructs, markedly higher glycosaminoglycan (GAG) contents were determined by histological and quantitative biochemical evaluation, both in normoxia and hypoxia. Differential GAG production was also reflected in layered co-culture constructs. For both cell types, similar staining for type II collagen was detected. However, distinctly weaker staining for undesired type I collagen was observed in the ACPC constructs. For ACPCs, only very low alkaline phosphatase (ALP) activity, a marker of terminal differentiation, was determined, in stark contrast to what was found for MSCs. This study underscores the potential of ACPCs as a promising cell source for cartilage engineering.
鉴定关节软骨祖细胞 (ACPCs) 为软骨修复开辟了新的机会。这些细胞可以替代或与软骨工程中的间充质基质细胞 (MSCs) 联合使用。然而,由于只有少数研究比较了在水凝胶中培养的 ACPCs 和 MSCs,因此它们的潜力需要进一步研究。因此,在这项研究中,我们比较了在琼脂糖构建体中单培养和分区层共培养条件下,正常氧和低氧条件下马 ACPCs 和 MSCs 的软骨分化。ACPCs 和 MSCs 表现出明显不同的软骨细胞外基质 (ECM) 产生。通过组织学和定量生化评估,在正常氧和低氧条件下,ACPC 构建体中均确定了明显更高的糖胺聚糖 (GAG) 含量。分层共培养构建体也反映了 GAG 的差异产生。对于这两种细胞类型,均检测到 II 型胶原的相似染色。然而,在 ACPC 构建体中观察到未期望的 I 型胶原染色明显较弱。对于 ACPCs,仅确定了非常低的碱性磷酸酶 (ALP) 活性,这是终末分化的标志物,与 MSCs 的情况形成鲜明对比。这项研究强调了 ACPCs 作为软骨工程有前途的细胞来源的潜力。