University Medical Centre Utrecht, Department of Oral and Maxillofacial Surgery and Special Dental Care, room G05.129, PO Box 85500, 3508 GA Utrecht, the Netherlands.
Eur Cell Mater. 2020 Feb 21;39:121-135. doi: 10.22203/eCM.v039a08.
Dental pulp stem cells (DPSCs) are particularly promising for tissue engineering (TE) due to the ease of their isolation procedure, great expansion potential and capability to differentiate towards several cell types of the mesodermal, ectodermal and endodermal lineages. Although several studies hint that DPSCs exhibit potential for cartilage tissue formation, the chondrogenic potential of DPSCs has only been marginally explored. Thus, the aim of the present study was to closely investigate the chondrogenic differentiation capacity of DPSCs for TE applications. More specifically, the potential of DPSCs for engineering hyaline and fibrous cartilage was determined. DPSCs obtained from 7 human molars were expanded and chondrogenically differentiated in a 3D pellet culture model. After 21 d of differentiation with chondrogenic stimuli, DPSCs displayed glycosaminoglycan, aggrecan and limited collagen type II deposition. Cells presented an elongated morphology and produced a collagen-rich extracellular matrix, with a predominance of collagen type I in most of the samples, a characteristic of fibrous cartilage tissue. Variations in the administration periods of several chondro-inductive growth factors, including transforming growth factor beta 3, bone morphogenetic protein-2, -6, -7 and insulin-like growth factor-1, did not increase glycosaminoglycan or collagen type II deposition, typical markers of hyaline cartilage tissue. Furthermore, DPSCs could not be stimulated to go into hypertrophic chondrogenesis. These results indicated that under a large variety of chondro-inductive culture conditions, DPSCs could form fibrocartilaginous tissues but not hyaline cartilage. Thus, DPSCs represent a valuable cell source for the regeneration of fibrocartilage in joints.
牙髓干细胞(DPSCs)由于其分离程序简单、具有巨大的扩增潜力并且能够向中胚层、外胚层和内胚层谱系的几种细胞类型分化,因此特别适用于组织工程(TE)。尽管有几项研究表明 DPSCs 具有形成软骨组织的潜力,但 DPSCs 的软骨形成潜力仅得到了初步探索。因此,本研究旨在深入研究 DPSCs 用于 TE 应用的软骨分化能力。更具体地说,确定了 DPSCs 用于工程透明软骨和纤维软骨的潜力。从 7 个人磨牙中获得的 DPSCs 在 3D 微球培养模型中进行扩增和软骨分化。在软骨诱导刺激下分化 21 天后,DPSCs 显示出糖胺聚糖、聚集蛋白聚糖和有限的胶原 II 沉积。细胞呈现出拉长的形态,并产生富含胶原的细胞外基质,大多数样本中胶原 I 占主导地位,这是纤维软骨组织的特征。改变几种软骨诱导生长因子(包括转化生长因子β 3、骨形态发生蛋白-2、-6、-7 和胰岛素样生长因子-1)的给药时间周期,并未增加糖胺聚糖或胶原 II 的沉积,这是透明软骨组织的典型标志物。此外,DPSCs 不能被刺激进入肥大性软骨形成。这些结果表明,在大量的软骨诱导培养条件下,DPSCs 可以形成纤维软骨组织,但不能形成透明软骨。因此,DPSCs 是关节中纤维软骨再生的有价值的细胞来源。