Preclinical study of mouse pluripotent parthenogenetic embryonic stem cell derivatives for the construction of tissue-engineered skin equivalent.
Preclinical study of mouse pluripotent parthenogenetic embryonic stem cell derivatives for the construction of tissue-engineered skin equivalent.
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小鼠多能孤雌胚胎干细胞衍生物构建组织工程皮肤等效物的临床前研究
DOI：
10.1186/s13287-016-0407-z
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发表时间：
2016-10-22
影响因子：
7.5
通讯作者：
Chen F
中科院分区：
文献类型：
--
作者：
Rao Y;Cui J;Yin L;Liu W;Liu W;Sun M;Yan X;Wang L;Chen F
背景胚胎干细胞（ESC）衍生物在构建组织工程皮肤（TESE）方面具有广阔的应用前景。然而，胚胎干细胞的收获破坏了可行的胚胎，并可能导致其应用的政治和伦理问题。在本研究中，我们指导小鼠孤雌胚胎干细胞（pESCs）分化为成纤维细胞，构建TESE，并评价其在体内的功能。经胚状体形成和贴壁培养后，间充质干细胞（MSCs）富集并定向分化为成纤维细胞系。通过定量实时PCR和ELISA评估衍生的成纤维细胞的特征。结果小鼠pESCs表达干细胞标记物，可形成含有三胚层的畸胎瘤。间充质干细胞可从EB的生长产物中富集并定向分化为成纤维细胞系。这些细胞表达高水平的生长因子，包括FGF、EGF、VEGF、TGF、PDGF和IGF1，类似于ESC衍生的成纤维细胞和小鼠成纤维细胞。将pESCs来源的成纤维细胞接种到胶原凝胶中，可以形成TESE。结论spESCs可诱导分化为成纤维细胞系，可应用于TESE的构建和皮肤缺损的修复。特别是，pESC衍生物避免了政治和伦理问题的限制，为再生医学提供了一个有前途的来源。
BackgroundEmbryonic stem cell (ESC) derivatives hold great promise for the construction of tissue-engineered skin equivalents (TESE). However, harvesting of ESCs destroys viable embryos and may lead to political and ethical concerns over their application. In the current study, we directed mouse parthenogenetic embryonic stem cells (pESCs) to differentiate into fibroblasts, constructed TESE, and evaluated its function in vivo.MethodsThe stemness marker expression and the pluripotent differentiation ability of pESCs were tested. After embryoid body (EB) formation and adherence culture, mesenchymal stem cells (MSCs) were enriched and directed to differentiate into fibroblastic lineage. Characteristics of derived fibroblasts were assessed by quantitative real-time PCR and ELISA. Functional ability of the constructed TESE was tested by a mouse skin defects repair model.ResultsMouse pESCs expressed stemness marker and could form teratoma containing three germ layers. MSCs could be enriched from outgrowths of EBs and directed to differentiate into fibroblastic lineage. These cells express a high level of growth factors including FGF, EGF, VEGF, TGF, PDGF, and IGF1, similar to those of ESC-derived fibroblasts and mouse fibroblasts. Seeded into collagen gels, the fibroblasts derived from pESCs could form TESE. Mouse skin defects could be successfully repaired 15 days after transplantation of TESE constructed by fibroblasts derived from pESCs.ConclusionspESCs could be induced to differentiate into fibroblastic lineage, which could be applied to the construction of TESE and skin defect repair. Particularly, pESC derivatives avoid the limitations of political and ethical concerns, and provide a promising source for regenerative medicine.
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DOI：
10.1073/pnas.1210422109
发表时间：
2012-11-20
影响因子：
11.1
作者：
Diekman, Brian O.;Christoforou, Nicolas;Guilak, Farshid
通讯作者：
Guilak, Farshid
影响因子：
--
作者：
Lampton PW;Crooker RJ;Newmark JA;Warner CM
通讯作者：
Warner CM
影响因子：
15.9
作者：
Didie, Michael;Christalla, Peter;Zimmermann, Wolfram-Hubertus
通讯作者：
Zimmermann, Wolfram-Hubertus
DOI：
10.1073/pnas.1201830109
发表时间：
2012-05-29
影响因子：
11.1
作者：
Marolt, Darja;Campos, Ivan Marcos;Vunjak-Novakovic, Gordana
通讯作者：
Vunjak-Novakovic, Gordana
影响因子：
5.2
作者：
Brederlau, Anke;Correia, Ana Sofia;Li, Jia-Yi
通讯作者：
Li, Jia-Yi