Extracellular Matrix from Periodontal Ligament Cells Could Induce the Differentiation of Induced Pluripotent Stem Cells to Periodontal Ligament Stem Cell-Like Cells
Extracellular Matrix from Periodontal Ligament Cells Could Induce the Differentiation of Induced Pluripotent Stem Cells to Periodontal Ligament Stem Cell-Like Cells
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DOI：
10.1089/scd.2017.0077
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发表时间：
2017-12-21
影响因子：
4
通讯作者：
Maeda, Hidefumi
中科院分区：
文献类型：
--
作者：
Hamano, Sayuri;Tomokiyo, Atsushi;Maeda, Hidefumi
牙周膜（PDL）在骨窝中起着锚定牙齿的重要作用。PDL的损伤，例如严重炎症后，可以用使用PDL组织来源的干细胞（PDLSC）的治疗策略进行治疗，这一策略在过去十年中受到了严格的审查。然而，PDL内的PDLSC数量不足以治疗这种损伤。因此，我们试图诱导诱导多能干细胞（iPS）分化为PDLSC作为PDL治疗的第一步。为此，我们首先将iPS细胞诱导为神经嵴（NC）样细胞。然后，我们捕获p75神经营养受体阳性细胞（iPS-NC细胞），并将其培养在由人PDL细胞（iPS-NC-PDL细胞）产生的细胞外基质（ECM）上。与iPS和iPS-NC细胞相比，这些iPS-NC-PDL细胞显示胚胎干细胞和NC细胞标志物的表达减少，并且间充质干细胞标志物富集。与在纤连蛋白和层粘连蛋白上培养的iPS-NC细胞（iPS-NC-FL细胞）或由人皮肤成纤维细胞产生的ECM（iPS-NC-SF细胞）相比，所述细胞还具有更高的增殖能力、多能性和PDL相关标志物的表达升高。总之，我们提出了一种培养方法，从iPS细胞产生大量的PDLSC样细胞作为PDL再生策略的第一步。
The periodontal ligament (PDL) plays an important role in anchoring teeth in the bone socket. Damage to the PDL, such as after severe inflammation, can be treated with a therapeutic strategy that uses stem cells derived from PDL tissue (PDLSCs), a strategy that has received intense scrutiny over the past decade. However, there is an insufficient number of PDLSCs within the PDL for treating such damage. Therefore, we sought to induce the differentiation of induced pluripotent stem (iPS) cells into PDLSCs as an initial step toward PDL therapy. To this end, we first induced iPS cells into neural crest (NC)-like cells. We then captured the p75 neurotrophic receptor-positive cells (iPS-NC cells) and cultured them on an extracellular matrix (ECM) produced by human PDL cells (iPS-NC-PDL cells). These iPS-NC-PDL cells showed reduced expression of embryonic stem cell and NC cell markers as compared with iPS and iPS-NC cells, and enrichment of mesenchymal stem cell markers. The cells also had a higher proliferative capacity, multipotency, and elevated expression of PDL-related markers than iPS-NC cells cultured on fibronectin and laminin (iPS-NC-FL cells) or ECM produced by human skin fibroblast cells (iPS-NC-SF cells). Overall, we present a culture method to produce high number of PDLSC-like cells from iPS cells as a first step toward a strategy for PDL regeneration.