Khajeh Sahar, Razban Vahid, Naeimzadeh Yasaman, Nadimi Elham, Asadi-Golshan Reza, Heidari Zahra, Talaei-Khozani Tahereh, Dehghani Farzaneh, Mostafavi-Pour Zohreh, Shirali Masoud
Bone and Joint Diseases Research Center, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran.
Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran.
Biology (Basel). 2024 Jul 24;13(8):560. doi: 10.3390/biology13080560.
The limited self-repair capacity of articular cartilage is a challenge for healing injuries. While mesenchymal stem/stromal cells (MSCs) are a promising approach for tissue regeneration, the criteria for selecting a suitable cell source remain undefined. To propose a molecular criterion, dental pulp stem cells (DPSCs) with a -negative expression pattern and bone marrow mesenchymal stromal cells (BMSCs), which actively express genes, were differentiated towards chondrocytes in 3D pellets, employing a two-step protocol. The MSCs' response to preconditioning by cobalt chloride (CoCl), a hypoxia-mimicking agent, was explored in an assessment of the chondrogenic differentiation's efficiency using morphological, histochemical, immunohistochemical, and biochemical experiments. The preconditioned DPSC pellets exhibited significantly elevated levels of collagen II and glycosaminoglycans (GAGs) and reduced levels of the hypertrophic marker collagen X. No significant effect on GAGs production was observed in the preconditioned BMSC pellets, but collagen II and collagen X levels were elevated. While preconditioning did not modify the ALP specific activity in either cell type, it was notably lower in the DPSCs differentiated pellets compared to their BMSCs counterparts. These results could be interpreted as demonstrating the higher plasticity of DPSCs compared to BMSCs, suggesting the contribution of their unique molecular characteristics, including their negative expression pattern, to promote a chondrogenic differentiation potential. Consequently, DPSCs could be considered compelling candidates for future cartilage cell therapy.
关节软骨有限的自我修复能力对损伤愈合而言是一项挑战。尽管间充质干/基质细胞(MSCs)是组织再生的一种有前景的方法,但选择合适细胞来源的标准仍不明确。为了提出一种分子标准,采用两步方案,将具有阴性表达模式的牙髓干细胞(DPSCs)和积极表达基因的骨髓间充质基质细胞(BMSCs)在三维微珠中向软骨细胞分化。在使用形态学、组织化学、免疫组织化学和生化实验评估软骨形成分化效率的过程中,探究了MSCs对氯化钴(CoCl)(一种模拟缺氧的试剂)预处理的反应。预处理后的DPSC微珠中II型胶原蛋白和糖胺聚糖(GAGs)水平显著升高,肥大标志物X型胶原蛋白水平降低。预处理后的BMSC微珠中未观察到对GAGs产生有显著影响,但II型胶原蛋白和X型胶原蛋白水平升高。虽然预处理对两种细胞类型的碱性磷酸酶(ALP)比活性均无影响,但与BMSC分化微珠相比,DPSC分化微珠中的ALP比活性明显更低。这些结果可以解释为表明DPSCs比BMSCs具有更高的可塑性,提示其独特的分子特征(包括其阴性表达模式)有助于促进软骨形成分化潜能。因此,DPSCs可被视为未来软骨细胞治疗的有力候选者。