Epithelial-stromal cell interactions and extracellular matrix mechanics drive the formation of airway-mimetic tubular morphology in lung organoids.
Epithelial-stromal cell interactions and extracellular matrix mechanics drive the formation of airway-mimetic tubular morphology in lung organoids.
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DOI：
10.1016/j.isci.2021.103061
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发表时间：
2021-09-24
期刊：
影响因子：
5.8
通讯作者：
Adcock IM
中科院分区：
文献类型：
--
作者：
Güney TG;Herranz AM;Mumby S;Dunlop IE;Adcock IM
细胞外基质(ECM)与上皮和基质细胞相互作用的复杂的人类呼吸道细胞组织为器官体外研究提出了挑战。目前，专注于肺上皮的体外肺模型并不能代表体内看到的复杂的呼吸道形态和细胞-ECM相互作用。包括基质种群在内的模型通常通过半渗透屏障将它们分开，从而排除细胞与细胞之间的相互作用或细胞外基质机制的影响。我们通过人支气管上皮细胞、肺成纤维细胞和气道平滑肌细胞的三重培养，研究了基质细胞对基础上皮细胞来源的支气管球结构和功能的影响。上皮-间质的相互作用导致上皮细胞驱动的分支小管，基质细胞包围上皮细胞，称为细支管。琼脂糖-Matrigel支架(Agrigel)形成了一种机械可调的ECM，具有可调节的粘弹性和硬度，使小管能够长期存活。细支管模型可能有助于研究上皮-间质细胞和细胞-ECM通讯如何驱动组织构型、修复和疾病的发展。健康的肺上皮细胞和成纤维细胞在Matrigel中共培养形成小管，4天内小管崩溃加入健康的呼吸道平滑肌细胞允许收缩表型在更坚硬的基质中三重培养保持管状器官结构20天生物工程；组织工程；生物技术；生物力学
Complex human airway cellular organization where extracellular matrix (ECM) and epithelial and stromal lineages interact present challenges for organ study in vitro. Current in vitro lung models that focus on the lung epithelium do not represent complex airway morphology and cell-ECM interactions seen in vivo. Models including stromal populations often separate them via a semipermeable barrier precluding cell–cell interaction or the effect of ECM mechanics. We investigated the effect of stromal cells on basal epithelial cell-derived bronchosphere structure and function through a triple culture of human bronchial epithelial, lung fibroblast, and airway smooth muscle cells. Epithelial–stromal cross-talk resulted in epithelial cell-driven branching tubules with stromal cells surrounding epithelial cells termed bronchotubules. Agarose– Matrigel scaffold (Agrigel) formed a mechanically tuneable ECM, with adjustable viscoelasticity and stiffness enabling long-term tubule survival. Bronchotubule models may enable research into how epithelial–stromal cell and cell–ECM communication drive tissue patterning, repair, and development of disease. Healthy lung epithelial and fibroblast cell coculture in Matrigel forms tubules Tubules collapse in 4 days Addition of healthy airway smooth muscle cells allows for a contractile phenotype Triple culture in stiffer matrix maintains tubular organoid structure for 20 days Bioengineering; Tissue engineering; Biotechnology; Biomechanics
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影响因子：
21.3
作者：
Chen YW;Huang SX;de Carvalho ALRT;Ho SH;Islam MN;Volpi S;Notarangelo LD;Ciancanelli M;Casanova JL;Bhattacharya J;Liang AF;Palermo LM;Porotto M;Moscona A;Snoeck HW
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影响因子：
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作者：
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影响因子：
76.2
作者：
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