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利用多能干细胞构建三维组织进行口腔黏膜修复的策略

Strategies for Oral Mucosal Repair by Engineering 3D Tissues with Pluripotent Stem Cells.

作者信息

Hewitt Kyle J, Shamis Yulia, Gerami-Naini Behzad, Garlick Jonathan A

机构信息

Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine , Boston, Massachusetts.

Department of Oral and Maxillofacial Pathology, Tufts University , Boston, Massachusetts.

出版信息

Adv Wound Care (New Rochelle). 2014 Dec 1;3(12):742-750. doi: 10.1089/wound.2013.0480.

DOI:10.1089/wound.2013.0480
PMID:25493208
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4250943/
Abstract

Human-induced pluripotent stem cells (iPSC) can be differentiated into patient-specific cells with a wide spectrum of cellular phenotypes and offer an alternative source of autologous cells for therapeutic use. Recent studies have shown that iPSC-derived fibroblasts display enhanced cellular functions suggesting that iPSC may eventually become an important source of stem cells for regenerative therapies. The discovery of approaches to reprogram somatic cells into pluripotent cells opens exciting avenues for their use in personalized, regenerative therapies. The controlled differentiation of functional cell types from iPSC provides a replenishing source of fibroblasts. There is intriguing evidence that iPSC reprogramming and subsequent differentiation to fibroblast lineages may improve cellular functional properties. Augmenting the biological potency of iPSC-derived fibroblasts may enable the development of novel, personalized stem cell therapies to treat oral disease. Numerous questions need to be addressed before iPSC-derived cells can be used as a practical oral therapy. This will include understanding why iPSC-derived cells are predisposed towards differentiation pathways along lineages related to their cell of origin, screening iPSC-derived cells to ensure their safety and phenotypic stability and developing engineered, three-dimensional tissue models to optimize their function and efficacy for future therapeutic transplantation. Future research will need to address how to develop efficient methods to deliver and integrate iPSC-derived fibroblasts into the oral mucosa. This will require an improved understanding of how to harness their biological potency for regenerative therapies that are specifically targeted to the oral mucosa.

摘要

人类诱导多能干细胞(iPSC)可以分化为具有广泛细胞表型的患者特异性细胞,并为治疗用途提供自体细胞的替代来源。最近的研究表明,iPSC来源的成纤维细胞表现出增强的细胞功能,这表明iPSC最终可能成为再生治疗中干细胞的重要来源。将体细胞重编程为多能细胞的方法的发现为其在个性化再生治疗中的应用开辟了令人兴奋的途径。从iPSC中可控地分化出功能细胞类型可提供成纤维细胞的补充来源。有有趣的证据表明,iPSC重编程以及随后向成纤维细胞谱系的分化可能会改善细胞功能特性。增强iPSC来源的成纤维细胞的生物学效力可能有助于开发新型的个性化干细胞疗法来治疗口腔疾病。在将iPSC来源的细胞用作实际的口腔治疗之前,需要解决许多问题。这将包括理解为什么iPSC来源的细胞倾向于沿着与其起源细胞相关的谱系的分化途径,筛选iPSC来源的细胞以确保其安全性和表型稳定性,以及开发工程化的三维组织模型以优化其功能和疗效以用于未来的治疗性移植。未来的研究将需要解决如何开发有效的方法来将iPSC来源的成纤维细胞递送并整合到口腔粘膜中。这将需要更好地理解如何利用它们的生物学效力来进行专门针对口腔粘膜的再生治疗。

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本文引用的文献

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Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds.小分子化合物诱导的小鼠体细胞多能干细胞。
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PLoS One. 2011 Feb 28;6(2):e17128. doi: 10.1371/journal.pone.0017128.
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