Biology subjects

Lehr, C.-M.

Publications and source records attributed to Lehr, C.-M..

3 recordsLinked to original sources

bioRxiv2025

Extracellular vesicles and their RNA cargo facilitate bidirectional cross-kingdom communication between human and bacterial cells

While extracellular vesicles (EVs) are established mediators of intra-species signaling, their role as active participants in cross-kingdom communication remains incompletely understood. Here, we reveal that human colon cells and both Gram-positive and Gram-negative gut bacteria engage in species-specific, EV-mediated molecular dialogue, driven in part by RNA cargo. We show that bacterial EVs (BEVs) induce distinct transcriptomic responses in human cells, and that BEV-RNA independently causes similar effects. Conversely, we demonstrate that human EVs and highly abundant miR-192-5p are differentially internalized by bacteria, affecting their physiology. Our findings support a conceptual model in which EVs function as directional messengers that shape host-microbiome interactions. This study introduces a framework for understanding EVs as cross-kingdom regulators and underscores the importance of tailored, context-specific analyses for understanding the scope of EV-mediated interactions in microbiome-host homeostasis and disease. Highlights[1] L. casei, E. faecalis and P. mirabilis produce BEVs that are internalized by Caco-2 cells at different rates. BEVs produced by L. casei have a positive influence on the viability of Caco-2 cells. Incubation of Caco-2 cells with BEVs leads to changes in the gene expression of immune-response-related genes. [2] BEVs carry RNAs and the type of RNA cargo varies significantly between the BEVs from the different bacteria. Comparison of Caco-2 gene deregulation between BEVs and transfection of RNA isolated from BEV highlights component-specific effects. [3] Caco-2 EVs are taken up by E. faecalis and influence their growth. MiRNA-192-5p can be frequently detected in EVs from Caco-2 cells. Synthetic miR-192-5p is internalized by P. mirabilis and the ability to take up human miRNAs by L. casei and E. faecalis can be increased by packaging of the miRNA in artificial liposomes.

molecular biology↗

bioRxiv2019

Second-generation lung-on-a-chip array with a stretchable biological membrane

The complex architecture of the lung parenchyma and the air-blood barrier is difficult to mimic in-vitro. Recently reported lung-on-a-chips used a thin, porous and stretchable PDMS membrane, to mimic the air-blood barrier and the rhythmic breathing motions. However, the nature, the properties and the size of this PDMS membrane differ from the extracellular matrix of the distal airways. Here, we present a second-generation lung-on-a-chip with an array of in vivo-like sized alveoli and a stretchable biological membrane. This nearly absorption free membrane allows mimicking in vivo functionality of the lung parenchyma at an unprecedented level. The air-blood barrier is constituted by human primary lung alveolar epithelial cells from several patients and co-cultured with primary lung endothelial cells. Typical markers of lung alveolar epithelial cells could be observed in the model, while barrier properties were preserved for up to three weeks. This advanced lung alveolar model reproduces some key features of the lung alveolar environment in terms of composition, alveolar size, mechanical forces and biological functions, which makes this model a more analogous tool for drug discovery, diseases modeling and precision medicine applications.

bioengineering↗

bioRxiv2017

Modified hCFTR mRNA restores normal lung function in a mouse model of cystic fibrosis

Being a classic monogenic disease, gene therapy has always been a promising therapeutic approach for Cystic Fibrosis (CF). However, numerous trials using DNA or viral vectors encoding the correct protein resulted in a general low efficacy. In the last years, chemically modified messenger RNA (cmRNA) has been proven to be a highly potent, pulmonary effective drug. We thus explored the expression of human (h)CFTR encoded by hCFTR cmRNA in vitro, analyzed by flow cytometry and Western Blot and its function with a YFP assay. Very similar effects could be observed in vivo when hCFTR cmRNA was assembled with Chitosan-coated PLGA to nanoparticles (NPs) and intratracheally (i.t.) or intravenously (i.v) injected, the latter one as an alternative administration route to circumvent the clogged airways of CF patients. This significantly improved lung function, which suggests that hCFTR cmRNA-NPs are a promising therapeutic option for CF patients independent of their CFTR genotype.

genetics↗