Microstructured Hydrogels to Guide Self-Assembly and Function of Lung Alveolospheres.

Microstructured Hydrogels to Guide Self-Assembly and Function of Lung Alveolospheres.
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微结构水凝胶引导肺泡球的自组装和功能。

DOI:
10.1002/adma.202202992
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发表时间:
2022-07
期刊:
影响因子:
29.4
通讯作者:
Burdick, Jason A.
Burdick, Jason A.
中科院分区:
材料科学1区
文献类型:
--
作者:
Loebel, Claudia;Weiner, Aaron, I;Eiken, Madeline K.;Katzen, Jeremy B.;Morley, Michael P.;Bala, Vikram;Cardenas-Diaz, Fabian L.;Davidson, Matthew D.;Shiraishi, Kazushige;Basil, Maria C.;Ferguson, Laura T.;Spence, Jason R.;Ochs, Matthias;Beers, Michael F.;Morrisey, Edward E.;Vaughan, Andrew E.;Burdick, Jason A.

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上皮细胞有机体有更多的机会探索组织发育和疾病的问题,并用于治疗性细胞移植。尽管它们具有潜力,但目前种植这些有机化合物的方案几乎完全依赖于三维(3D)Matrigel中的培养,这限制了确定的培养条件,引入了动物成分,并导致了异质有机物(即形状、大小、组成)。在这里,我们描述了一种依赖于聚合物水凝胶底物来产生和扩张肺泡有机体(肺泡球)的方法。利用具有特定化学和物理特性的合成水凝胶,人类诱导的多能干细胞(IPSC)来源的肺泡2型细胞(IAT2s)自组装成肺泡球,并在无Matrigel的条件下繁殖。通过在这些水凝胶中设计预定义的微腔,与3D培养相比,降低了肺泡球大小和结构的异质性,同时保持了人iAT2来源的祖细胞的肺泡2型细胞命运。该水凝胶体系是一种简便、易获得的培养IPSC来源的肺祖细胞的培养系统,该方法可扩展到原代小鼠组织来源的AT2和其他上皮祖细胞和干细胞聚集体的培养。上皮细胞有机体为体外和细胞移植提供了一种探测组织发育和疾病的系统。肺泡内的有机体几乎完全依赖于Matrigel,这限制了确定的培养条件。在这里,我们描述了一种可访问的水凝胶系统的设计,该系统具有预先定义的微腔,通过自组装和维持祖细胞的命运和功能来产生肺泡有机物质。
Epithelial cell organoids have increased opportunities to probe questions on tissue development and disease in vitro and for therapeutic cell transplantation. Despite their potential, current protocols to grow these organoids almost exclusively depend on culture within three-dimensional (3D) Matrigel, which limits defined culture conditions, introduces animal components, and results in heterogenous organoids (i.e., shape, size, composition). Here, we describe a method that relies on polymeric hydrogel substrates for the generation and expansion of lung alveolar organoids (alveolospheres). Using synthetic hydrogels with defined chemical and physical properties, human induced pluripotent stem cell (iPSC)-derived alveolar type 2 cells (iAT2s) self-assemble into alveolospheres and propagate in Matrigel-free conditions. By engineering pre-defined microcavities within these hydrogels, the heterogeneity of alveolosphere size and structure is reduced when compared to 3D culture, while maintaining alveolar type 2 cell fate of human iAT2-derived progenitor cells. This hydrogel system is a facile and accessible culture system for the culture of iPSC-derived lung progenitors and the method can be expanded to the culture of primary mouse tissue-derived AT2 and other epithelial progenitor and stem cell aggregates. Epithelial cell organoids provide a system to probe tissue development and disease in vitro and for cell transplantation. Within the lung alveolar organoids almost exclusively depend on Matrigel, which limits defined culture conditions. Here, we describe the design of an accessible hydrogel system with pre-defined microcavities to generate alveolar organoids through self-assembly and maintenance of progenitor cell fate and function.
DOI: 10.1038/s41578-021-00279-y
发表时间: 2021
期刊: Nature reviews. Materials
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影响因子: 6.4
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