Influence of Acellular Natural Lung Matrix on Murine Embryonic Stem Cell Differentiation and Tissue Formation
Influence of Acellular Natural Lung Matrix on Murine Embryonic Stem Cell Differentiation and Tissue Formation
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DOI：
10.1089/ten.tea.2009.0730
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发表时间：
2010-08-01
影响因子：
4.1
通讯作者：
Nichols, Joan E.
中科院分区：
文献类型：
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作者：
Cortiella, Joaquin;Niles, Jean;Nichols, Joan E.
我们在此报道首次尝试制备并使用全脱细胞（AC）肺作为基质，以支持从鼠胚胎干细胞（mESCs）构建工程化肺组织。我们比较了AC肺、明胶海绵、基质胶以及I型胶原水凝胶基质对mESC的附着、分化以及后续复杂组织形成的影响。我们发现AC肺能更好地保留细胞，且能使更多的mESCs分化为上皮和内皮谱系。在全AC肺上构建的组织中，我们看到了分化的ESC组织成三维结构的迹象，类似于复杂组织。我们还观察到甲状腺转录因子 - 1（一种未成熟肺上皮细胞标志物）、表面活性蛋白C前体（一种II型肺细胞标志物）、血小板内皮细胞粘附分子 - 1/CD31（一种内皮细胞标志物）、细胞角蛋白18、α - 肌动蛋白（一种平滑肌标志物）、CD140a或血小板衍生生长因子受体 - α以及克拉拉细胞蛋白10的表达。还有证据表明在气管中存在位点特异性分化，形成了细胞角蛋白阳性细胞片和表达克拉拉细胞蛋白10的克拉拉细胞。我们的研究结果支持AC肺作为工程化肺组织基质的实用性，并强调了基质或支架相关线索在引导ESC向肺特异性谱系分化中所起的关键作用。
We report here the first attempt to produce and use whole acellular (AC) lung as a matrix to support development of engineered lung tissue from murine embryonic stem cells (mESCs). We compared the influence of AC lung, Gelfoam, Matrigel, and a collagen I hydrogel matrix on the mESC attachment, differentiation, and subsequent formation of complex tissue. We found that AC lung allowed for better retention of cells with more differentiation of mESCs into epithelial and endothelial lineages. In constructs produced on whole AC lung, we saw indications of organization of differentiating ESC into three-dimensional structures reminiscent of complex tissues. We also saw expression of thyroid transcription factor-1, an immature lung epithelial cell marker; prosurfactant protein C, a type II pneumocyte marker; PECAM-1/CD31, an endothelial cell marker; cytokeratin 18; a-actin, a smooth muscle marker; CD140a or platelet-derived growth factor receptor-alpha; and Clara cell protein 10. There was also evidence of site-specific differentiation in the trachea with the formation of sheets of cytokeratin-positive cells and Clara cell protein 10-expressing Clara cells. Our findings support the utility of AC lung as a matrix for engineering lung tissue and highlight the critical role played by matrix or scaffold-associated cues in guiding ESC differentiation toward lung-specific lineages.