Therapeutics & Biomarker Discovery for Clinical Applications, Stem Cell & Tissue Re-Engineering Program, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
Department of Dentistry, King Faisal Specialist Hospital & Research Center, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
Int J Mol Sci. 2020 Dec 31;22(1):380. doi: 10.3390/ijms22010380.
Osteopetrosis is a hereditary disorder characterized by sclerotic, thick, weak, and brittle bone. The biological behavior of mesenchymal cells obtained from osteopetrosis patients has not been well-studied. Isolated mesenchymal stem/stromal cells from dental pulp (DP-MSSCs) of recently extracted deciduous teeth from osteopetrosis (OP) patients and healthy controls (HCs) were compared. We evaluated whether the dental pulp of OP patients has a population of MSSCs with similar multilineage differentiation capability to DP-MSSCs of healthy subjects. Stem/progenitor cells were characterized using immunohistochemistry, flow cytometry, and proteomics. Our DP-MSSCs were strongly positive for CD44, CD73, CD105, and CD90. DP-MSSCs obtained from HC subjects and OP patients showed similar patterns of proliferation and differentiation as well as gene expression. Proteomic analysis identified 1499 unique proteins with 94.3% similarity in global protein fingerprints of HCs and OP patients. Interestingly, we observed subtle differences in expressed proteins of osteopetrosis disease-related in pathways, including MAPK, ERK 1/2, PI3K, and integrin, rather than in the stem cell signaling network. Our findings of similar protein expression signatures in DP-MSSCs of HC and OP patients are of paramount interest, and further in vivo validation study is needed. There is the possibility that OP patients could have their exfoliating deciduous teeth banked for future use in regenerative dentistry.
骨硬化病是一种遗传性疾病，其特征为骨硬化、增厚、脆弱和易碎。骨硬化病患者间充质细胞的生物学行为尚未得到很好的研究。本研究比较了取自骨硬化病（OP）患者和健康对照者（HC）近期拔除的乳牙牙髓中的分离间充质干细胞（DP-MSSC）。我们评估了 OP 患者的牙髓是否存在具有与健康供体 DP-MSSC 相似的多能分化能力的 MSSC 群体。采用免疫组化、流式细胞术和蛋白质组学对干细胞/祖细胞进行了鉴定。我们的 DP-MSSC 强烈表达 CD44、CD73、CD105 和 CD90。来自 HC 受试者和 OP 患者的 DP-MSSC 显示出相似的增殖和分化模式以及基因表达。蛋白质组学分析鉴定了 1499 种独特的蛋白质，其在 HC 和 OP 患者的全局蛋白质指纹图谱中具有 94.3%的相似性。有趣的是，我们观察到骨硬化病相关通路中表达蛋白存在细微差异，包括 MAPK、ERK1/2、PI3K 和整合素，而不是在干细胞信号网络中。我们发现 HC 和 OP 患者的 DP-MSSC 具有相似的蛋白质表达特征，这非常有趣，需要进一步进行体内验证研究。OP 患者有可能为未来再生牙科而储存其正在脱落的乳牙。
