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Explant-derived human dental pulp stem cells enhance differentiation and proliferation potentials

机译:外植体来源的人类牙髓干细胞增强分化和增殖潜能

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摘要

Numerous stem cell niches are present in the different tissues and organs of the adult human body. Among these tissues, dental pulp, entrapped within the ‘sealed niche’ of the pulp chamber, is an extremely rich site for collecting stem cells. In this study, we demonstrate that the isolation of human dental pulp stem cells by the explants culture method (hD-DPSCs) allows the recovery of a population of dental mesenchymal stem cells that exhibit an elevated proliferation potential. Moreover, we highlight that hD-DPSCs are not only capable of differentiating into osteoblasts and chondrocytes but are also able to switch their genetic programme when co-cultured with murine myoblasts. High levels of MyoD expression were detected, indicating that muscle-specific genes in dental pulp cells can be turned on through myogenic fusion, confirming thus their multipotency. A perivascular niche may be the potential source of hD-DPSCs, as suggested by the consistent Ca2+ release from these cells in response to endothelin-1 (ET-1) treatment, which is also able to significantly increase cell proliferation. Moreover, response to ET-1 has been found to be superior in hD-DPSCs than in DPSCs, probably due to the isolation method that promotes release of stem/progenitor cells from perivascular structures. The ability to isolate, expand and direct the differentiation of hD-DPSCs into several lineages, mainly towards myogenesis, offers an opportunity for the study of events associated with cell commitment and differentiation. Therefore, hD-DPSCs display enhanced differentiation abilities when compared to DPSCs, and this might be of relevance for their use in therapy.
机译:成年人体的不同组织和器官中存在许多干细胞壁ni。在这些组织中,残留在牙髓腔“封闭壁iche”中的牙髓是收集干细胞的极为丰富的场所。在这项研究中,我们证明了通过外植体培养方法(hD-DPSCs)分离人牙髓干细胞可以恢复具有较高增殖潜能的牙齿间充质干细胞。此外,我们强调hD-DPSCs不仅能够分化为成骨细胞和软骨细胞,而且与鼠成肌细胞共培养时还能够切换其遗传程序。检测到高水平的MyoD表达,表明牙髓细胞中的肌肉特异性基因可以通过肌原性融合而开启,从而证实了它们的多能性。血管内皮生态位可能是hD-DPSCs的潜在来源,这是由于内皮素-1(ET-1)处理从这些细胞中持续释放的Ca 2 + 所暗示的,这也能够显着增加细胞增殖。此外,已发现hD-DPSC中对ET-1的反应优于DPSC,这可能是由于分离方法促进了血管周围结构中干细胞/祖细胞的释放。将hD-DPSCs的分离,扩展和定向分化为几个谱系的能力(主要是针对肌发生),为研究与细胞定型和分化相关的事件提供了机会。因此,与DPSC相比,hD-DPSC显示出增强的分化能力,这可能与其在治疗中的用途有关。

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