Neural crest-derived cells possess differentiation potential to keratinocytes in the process of wound healing
Neural crest-derived cells possess differentiation potential to keratinocytes in the process of wound healing
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DOI：
10.1016/j.biopha.2021.112593
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发表时间：
2021-12-28
影响因子：
7.5
通讯作者：
Takami，Masamichi
中科院分区：
文献类型：
--
作者：
Takizawa，Hideomi;Karakawa，Akiko;Takami，Masamichi
神经嵴衍生细胞（NCDC），在胎儿期以神经嵴细胞的形式存在，并分化为腭细胞，也存在于成人腭组织中，但作用未知。本研究以P0-Cre/CAG-CAT-EGFP（P0-EGFP）双转基因小鼠的NCDCs为研究对象，分析其在腭黏膜创伤愈合中的作用。作为腭部创伤愈合模型，切除P0-EGFP小鼠左侧腭部粘膜，检测愈合区干细胞标志物和角质形成细胞标志物。从正常腭粘膜中提取NCDCs，用干细胞培养基预培养14天，然后分化为角质形成细胞或成骨细胞以分析多能性。伤口愈合过程在第2天开始于边缘粘膜再生，并且在第28天整个伤口区域由具有EGFP阳性细胞（NCDC）的再生粘膜衬里。EGFP阳性细胞约占愈合口腔粘膜细胞的60%，其中65%表达干细胞标志物（Sca-1+，PDGFRα+），30%表达角质形成细胞标志物（CK 13+）。在培养的腭粘膜细胞的测试中，约70%的EGFP阳性细胞表达干细胞标志物（Sca-1+，PDGFRα+）。此外，在分化诱导条件下，培养的EGFP阳性细胞被成功诱导分化为角质形成细胞和成骨细胞。我们的结论是NCDCs作为干细胞存在于成人腭组织中，并且在伤口愈合过程中具有分化成各种细胞类型的潜力。
Neural crest-derived cells (NCDCs), which exist as neural crest cells during the fetal stage and differentiate into palate cells, also exist in adult palate tissues, though with unknown roles. In the present study, NCDCs were labeled with EGFP derived from P0-Cre/CAG-CAT-EGFP (P0-EGFP) double transgenic mice, then their function in palate mucosa wound healing was analyzed. As a palate wound healing model, left-side palate mucosa of P0-EGFP mice was resected, and stem cell markers and keratinocyte markers were detected in healed areas. NCDCs were extracted from normal palate mucosa and precultured with stem cell media for 14 days, then were differentiated into keratinocytes or osteoblasts to analyze pluripotency. The wound healing process started with marginal mucosal regeneration on day two and the entire wound area was lined by regenerated mucosa with EGFP-positive cells (NCDCs) on day 28. EGFP-positive cells comprised approximately 60% of cells in healed oral mucosa, and 65% of those expressed stem cell markers (Sca-1+, PDGFRα+) and 30% expressed a keratinocyte marker (CK13+). In tests of cultured palate mucosa cells, approximately 70% of EGFP-positive cells expressed stem cell markers (Sca-1+, PDGFRα+). Furthermore, under differentiation inducing conditions, cultured EGFP-positive cells were successfully induced to differentiate into keratinocytes and osteoblasts. We concluded that NCDCs exist in adult palate tissues as stem cells and have potential to differentiate into various cell types during the wound healing process.