Testing of drugs using human feto-maternal interface organ-on-chips provide insights into pharmacokinetics and efficacy

使用人类胎儿-母体界面器官芯片进行药物测试,可以深入了解药代动力学和疗效

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作者:Lauren S Richardson, Ananth K Kammala, Maged M Costantine, Stephen J Fortunato, Enkhtuya Radnaa, Sungjin Kim, Robert N Taylor, Arum Han, Ramkumar Menon

Conclusion

Two distinct feto-maternal interface OOCs were developed, tested, and validated for their utility to conduct preclinical trials during pregnancy. We demonstrated that the placenta and fetal membranes-decidual interface both are able to transport and metabolize drugs and that the safety and efficacy of a drug can be determined using the anatomical structures recreated on OOCs.

Results

Both OOCs mimicked two distinct human feto-maternal interfaces. The drugs tested permeated the maternal-fetal cell layers of the FMi-OOC and PLA-OOC within 4 hours and generated cell and time-specific statin metabolites from various cell types without causing any cytotoxicity. OS-induced pro-inflammatory cytokines were effectively reduced by statins by increasing anti-inflammatory cytokine response across the FMi-OOC and PLA-OOC.

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