Electrical stimulation induces direct reprogramming of human dermal fibroblasts into hyaline chondrogenic cells
Electrical stimulation induces direct reprogramming of human dermal fibroblasts into hyaline chondrogenic cells
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DOI：
10.1016/j.bbrc.2019.04.027
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发表时间：
2019-06-11
影响因子：
3.1
通讯作者：
Kwon, Hyuck Joon
中科院分区：
文献类型：
--
作者：
Lee, Gyu Seok;Kim, Min Gu;Kwon, Hyuck Joon
关节软骨的修复需要足够数量的软骨细胞来替代缺损组织。直接将成纤维细胞重编程为软骨细胞可以提供足够数量的软骨细胞，因为成纤维细胞可以有效地扩增。在此，我们首次证明电刺激可以驱动人类真皮成纤维细胞（HDFs）直接重编程为透明软骨细胞。我们的研究结果表明，在不添加外源生长因子或基因转导的情况下，电刺激驱动HDFs的冷凝，然后提高软骨形成标志物（如II型胶原、聚集蛋白和Sox9）的表达水平，并降低I型胶原的表达水平。电刺激-直接重编程的软骨细胞显示正常核型。我们还发现电刺激增加了TGF-betal、PDGF-AA和igfbp - 2,3的分泌水平。这些发现不仅有助于直接重编程的新方法，而且有助于软骨再生的细胞治疗。(C) 2019 Elsevier Inc.版权所有。
The repair of articular cartilage needs a sufficient number of chondrocytes to replace the defect tissue. Direct reprogramming of fibroblasts into chondrocytes can provide a sufficient number of chondrocytes because fibroblasts can be expanded efficiently. Herein, we demonstrate for the first time that electrical stimulation can drive direct reprogramming of human dermal fibroblasts (HDFs) into hyaline chondrogenic cells. Our results shows that electrical stimulation drives condensation of HDFs and then enhances expression levels of chondrogenic markers, such as type II collagen, aggrecan, and Sox9, and decreases type I collagen levels without the addition of exogenous growth factors or gene transduction. Electrical stimulation-directly reprogrammed chondrogenic cells showed the normal karyotype. It was also found that electrical stimulation increased the secretion levels of TGF-betal, PDGF-AA, and IGFBP-2, 3. These findings may contribute to not only novel approach of direct reprogramming but also cell therapy for cartilage regeneration. (C) 2019 Elsevier Inc. All rights reserved.