In vitro models for lactation studies

Informed decisions about medicines during breastfeeding require evidence of how chemical compounds are transferred to milk. The ConcePTION project has developed a non-clinical framework to support data generation about the exposure-related safety of maternal medicines for lactating mothers. The first pillar of this framework is in vitro models for the blood-milk barrier, which offer the possibility of screening the milk transfer of medicines in early drug development stages.

The ConcePTION in vitro models to study the blood-milk barrier rely on human mammary epithelial cells (hMECs) and minipig mammary epithelial cells (mpMECs). In-dept characterization of both cell culture assays indicate that the models are promising tools to study the medicine partitioning in human milk. Efforts to evaluate the predictive performance of the models towards the human in vivo milk-to-plasma ratio are ongoing and will be published after the ConcePTION project ends.

In addition to the in vitro models, the ConcePTION non-clinical framework for lactation studies includes in vivo models and in silico (PB/PK) models. The project has also developed a framework for clinical lactation studies.

Publications

La Mantia D, Nauwelaerts N, Bernardini C, Zannoni A, Salaroli R, Lin Q, Huys I, Annaert P, Forni M. Development and Characterization of a Human Mammary Epithelial Cell Culture Model for the Blood-Milk Barrier-A Contribution from the ConcePTION Project. Int J Mol Sci. 2024 Oct 25;25(21):11454. doi: 10.3390/ijms252111454. PMID: 39519007.

Bernardini C, Nesci S, La Mantia D, Salaroli R, Nauwelaerts N, Ventrella D, Elmi A, Trombetti F, Zannoni A, Forni M. Isolation and characterization of mammary epithelial cells derived from Göttingen Minipigs: A comparative study versus hybrid pig cells from the IMI-ConcePTION Project. Res Vet Sci. 2024 Jun;172:105244. doi: 10.1016/j.rvsc.2024.105244. Epub 2024 Mar 27. PMID: 38554548.

Bernardini C, La Mantia D, Salaroli R, Zannoni A, Nauwelaerts N, Deferm N, Ventrella D, Bacci ML, Sarli G, Bouisset-Leonard M, Annaert P, Forni M. Development of a Pig Mammary Epithelial Cell Culture Model as a Non-Clinical Tool for Studying Epithelial Barrier-A Contribution from the IMI-ConcePTION Project. Animals (Basel). 2021 Jul 5;11(7):2012. doi: 10.3390/ani11072012. PMID: 34359140; PMCID: PMC8300391.

Nauwelaerts N, Deferm N, Smits A, Bernardini C, Lammens B, Gandia P, Panchaud A, Nordeng H, Bacci ML, Forni M, Ventrella D, Van Calsteren K, DeLise A, Huys I, Bouisset-Leonard M, Allegaert K, Annaert P. A comprehensive review on non-clinical methods to study transfer of medication into breast milk – A contribution from the ConcePTION project. Biomed Pharmacother. 2021 Apr;136:111038. doi: 10.1016/j.biopha.2020.111038. Epub 2021 Jan 30. PMID: 33526310.