Rapid 3D bioprinting of a multicellular model recapitulating pterygium microenvironment.

Rapid 3D bioprinting of a multicellular model recapitulating pterygium microenvironment.
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DOI:
10.1016/j.biomaterials.2022.121391
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发表时间:
2022-03
期刊:
影响因子:
14
通讯作者:
--
中科院分区:
工程技术1区
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--
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翼状胬肉是一种高患病率的眼表疾病,可导致视力损害。翼状胬肉是结膜的病理性生长,涉及新生血管和慢性炎症。在这里,我们使用基于数字光处理(DLP)的3D生物打印平台与人结膜干细胞(hCjSC)开发了3D多细胞体外翼状胬肉模型。采用一种新型的无饲养层培养系统,有效地扩增了具有同质性、干细胞性和分化潜能的原代hCjSC。基于DLP的3D生物打印方法能够制造支持封装的hCjSC的活力和生物完整性的水凝胶支架。生物打印的3D翼状胬肉模型由hCjSC、免疫细胞和血管细胞组成,以重现疾病微环境。使用RNA测序(RNA-seq)的转录组学分析在生物打印的3D翼状胬肉模型中鉴定了与炎症反应、血管生成和上皮间质转化相关的独特谱。此外,生物打印模型的翼状胬肉特征和疾病相关性用来自患者来源的翼状胬肉组织的公开RNA-seq数据进行了验证。通过将干细胞技术与3D生物打印相结合,这是第一个报道的翼状胬肉3D体外疾病模型,可用于未来的个性化医学和药物筛选研究。
Pterygium is an ocular surface disorder with high prevalence that can lead to vision impairment. As a pathological outgrowth of conjunctiva, pterygium involves neovascularization and chronic inflammation. Here, we developed a 3D multicellular in vitro pterygium model using a digital light processing (DLP)-based 3D bioprinting platform with human conjunctival stem cells (hCjSCs). A novel feeder-free culture system was adopted and efficiently expanded the primary hCjSCs with homogeneity, stemness and differentiation potency. The DLP-based 3D bioprinting method was able to fabricate hydrogel scaffolds that support the viability and biological integrity of the encapsulated hCjSCs. The bioprinted 3D pterygium model consisted of hCjSCs, immune cells, and vascular cells to recapitulate the disease microenvironment. Transcriptomic analysis using RNA sequencing (RNA-seq) identified a distinct profile correlated to inflammation response, angiogenesis, and epithelial mesenchymal transition in the bioprinted 3D pterygium model. In addition, the pterygium signatures and disease relevance of the bioprinted model were validated with the public RNA-seq data from patient-derived pterygium tissues. By integrating the stem cell technology with 3D bioprinting, this is the first reported 3D in vitro disease model for pterygium that can be utilized for future studies towards personalized medicine and drug screening.
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