Diomede Francesca, Rajan Thangavelu Soundara, Gatta Valentina, D'Aurora Marco, Merciaro Ilaria, Marchisio Marco, Muttini Aurelio, Caputi Sergio, Bramanti Placido, Mazzon Emanuela, Trubiani Oriana
Stem Cells and Regenerative Medicine Laboratory, Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio", Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy.
Stem Cells Int. 2017;2017:5651287. doi: 10.1155/2017/5651287. Epub 2017 Apr 2.
. Neural crest-derived mesenchymal stem cells (MSCs) from human oral tissues possess immunomodulatory and regenerative properties and are emerging as a potential therapeutic tool to treat diverse diseases, such as multiple sclerosis, myocardial infarction, and connective tissue damages. In addition to cell-surface antigens, dental MSCs express embryonic stem cell markers as neural crest cells originate from the ectoderm layer. In vitro passages may eventually modify these embryonic marker expressions and other stemness properties, including proliferation. In the present study, we have investigated the expression of proteins involved in cell proliferation/senescence and embryonic stem cell markers during early (passage 2) and late passages (passage 15) in MSCs obtained from human gingiva, periodontal, and dental pulp tissues. . Cell proliferation assay, beta galactosidase staining, immunocytochemistry, and real-time PCR techniques were applied. . Cell proliferation assay showed no difference between early and late passages while senescence markers p16 and p21 were considerably increased in late passage. Embryonic stem cell markers including SKIL, MEIS1, and JARID2 were differentially modulated between P2 and P15 cells. . Our results suggest that the presence of embryonic and proliferation markers even in late passage may potentially endorse the application of dental-derived MSCs in stem cell therapy-based clinical trials.
来自人类口腔组织的神经嵴源性间充质干细胞(MSCs)具有免疫调节和再生特性,正逐渐成为治疗多种疾病的潜在治疗工具,如多发性硬化症、心肌梗死和结缔组织损伤。除了细胞表面抗原外,牙源性间充质干细胞还表达胚胎干细胞标志物,因为神经嵴细胞起源于外胚层。体外传代最终可能会改变这些胚胎标志物的表达以及其他干性特性,包括增殖。在本研究中,我们调查了从人牙龈、牙周和牙髓组织获得的间充质干细胞在早期传代(第2代)和晚期传代(第15代)期间参与细胞增殖/衰老的蛋白质表达以及胚胎干细胞标志物。应用了细胞增殖测定、β-半乳糖苷酶染色、免疫细胞化学和实时PCR技术。细胞增殖测定显示早期和晚期传代之间没有差异,而衰老标志物p16和p21在晚期传代中显著增加。包括SKIL、MEIS1和JARID2在内的胚胎干细胞标志物在第2代和第15代细胞之间受到不同的调节。我们的结果表明,即使在晚期传代中存在胚胎和增殖标志物,也可能支持牙源性间充质干细胞在基于干细胞治疗的临床试验中的应用。