Bioprinting of dual ECM scaffolds encapsulating limbal stem/progenitor cells in active and quiescent statuses.
Bioprinting of dual ECM scaffolds encapsulating limbal stem/progenitor cells in active and quiescent statuses.
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DOI：
10.1088/1758-5090/ac1992
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发表时间：
2021-08-13
期刊：
影响因子：
9
通讯作者：
Chen S
中科院分区：
文献类型：
--
作者：
Zhong Z;Balayan A;Tian J;Xiang Y;Hwang HH;Wu X;Deng X;Schimelman J;Sun Y;Ma C;Dos Santos A;You S;Tang M;Yao E;Shi X;Steinmetz NF;Deng SX;Chen S
角膜缘干细胞缺乏症（LSCD）和角膜疾病是人类视力的全球最大威胁之一。将干细胞移植与工程水凝胶支架结合起来用于生物和机械支持的新兴疗法正在成为该领域的一个上升趋势。然而，用于高通量制造水凝胶支架的方法，以及角膜缘干/祖细胞（LSC）与周围细胞外基质（ECM）之间的相互作用的知识仍然是非常需要的。在这里，我们采用基于数字光处理（DLP）的生物打印来制造封装原代LSC的水凝胶支架，并研究ECM依赖的LSC表型。使用明胶甲基丙烯酸酯（GelMA）或透明质酸甲基丙烯酸缩水甘油酯（HAGM）的基于DLP的生物打印产生了微尺度水凝胶支架，其可以支持包封的原代兔LSC（rbLSC）在培养物中的活力。免疫细胞化学和转录分析表明，封装的rbLSCs在基于GelMA的支架中保持活性，而在基于HAGM的支架中表现出静止。包封在生物打印支架内的原代人LSC（hLSC）显示出一致的ECM依赖性活性/静止状态。基于这些结果，我们开发了一种新型的生物打印双ECM“阴阳”模型，该模型封装LSC以支持活动和静止状态。我们的发现为干细胞疗法和角膜重建的再生医学提供了有价值的见解。
Limbal stem cell deficiency (LSCD) and corneal disorders are among the top global threats for human vision. Emerging therapies that integrate stem cell transplantation with engineered hydrogel scaffolds for biological and mechanical support are becoming a rising trend in the field. However, methods for high-throughput fabrication of hydrogel scaffolds, as well as knowledge of the interaction between limbal stem/progenitor cells (LSCs) and the surrounding extracellular matrix (ECM) are still much needed. Here, we employed digital light processing (DLP)-based bioprinting to fabricate hydrogel scaffolds encapsulating primary LSCs and studied the ECM-dependent LSC phenotypes. The DLP-based bioprinting with gelatin methacrylate (GelMA) or hyaluronic acid glycidyl methacrylate (HAGM) generated microscale hydrogel scaffolds that could support the viability of the encapsulated primary rabbit LSCs (rbLSCs) in culture. Immunocytochemistry and transcriptional analysis showed that the encapsulated rbLSCs remained active in GelMA-based scaffolds while exhibited quiescence in the HAGM-based scaffolds. The primary human LSCs (hLSCs) encapsulated within bioprinted scaffolds showed consistent ECM-dependent active/quiescent statuses. Based on these results, we have developed a novel bioprinted dual ECM ‘Yin-Yang’ model encapsulating LSCs to support both active and quiescent statues. Our findings provide valuable insights towards stem cell therapies and regenerative medicine for corneal reconstruction.
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DOI：
10.1158/1541-7786.mcr-13-0629
发表时间：
2014-10
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Kim Y;Kumar S
通讯作者：
Kumar S
DOI：
10.1016/j.jtos.2017.11.002
发表时间：
2018-01
期刊：
The ocular surface
影响因子：
--
作者：
Le Q;Xu J;Deng SX
通讯作者：
Deng SX
影响因子：
3
作者：
Gouveia RM;Connon CJ
通讯作者：
Connon CJ
DOI：
10.1083/jcb.200703003
发表时间：
2007-06-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Barbaro V;Testa A;Di Iorio E;Mavilio F;Pellegrini G;De Luca M
通讯作者：
De Luca M
影响因子：
4.4
作者：
Hopkinson, Andrew;McIntosh, Richard S.;Dua, Harminder S.
通讯作者：
Dua, Harminder S.