Cellular Communication

During pregnancy, a special organ is formed: the placenta. Its main purpose is to transport oxygen and nutrients from the mother to the baby and allow excretion of waste products from the baby via the mother. It is also an immune organ that promotes successful pregnancy and an endocrine organ that facilitates necessary adaptations of maternal metabolism during the course of pregnancy.

Placenta is also a multi-cellular organ consisting of various cell types, and we aim to understand how these cell types interact and communicate with one another to promote proper placental development.

Moreover, cells have been demonstrated to send out small messengers, e.g. microRNAs and extracellular vesicles, and we want to find out how these messengers allow communication between mother and baby and how these communication pathways are changed in pregnancies affected by e.g. pre-eclampsia.

Interaction between Macrophages and Endothelial cells in placental angiogenesis

Carolin Schliefsteiner - Teammitglied bei PlancentaLab

Carolin Schliefsteiner
PhD, PI

Macrophages are highly plastic cells. In placenta, they are the main immune cells, but fulfil many more functions in addition. E.g., they promote fetal tolerance in the mother, they regulate tissue homeostasis and remodeling. They are known to interact with trophoblast cells to modulate the extracellular matrix and thereby allow for proper trophoblast invasion. It also has been suggested in the past, that they interact with endothelial cell, remodelling the ECM to allow for angiogenic sprouting and new blood vessel growth.

Here, we investigate how macrophages might influence endothelial cell angiogenesis using both primary Hofbauer cells and feto-placental endothelial cells isolated from placenta. As mono-culture of a single cell types in vitro is a quite artificial set-up, our aim is to establish a co-culture model of endothelial cells and macrophages and use it in functional assays of angiogenesis, to resemble the in vivo situation more closely. As angiogenesis and endothelial function in placenta from pregnancies compromised by pre-eclampsia or diabetes differs from that of healthy pregnancies, investigation of endothelial and macrophage function in such pathologies is essential, too.

Schliefsteiner C, Peinhaupt M, Kopp S, Lögl J, Lang-Olip I, Hiden U, Heinemann A, Desoye G, Wadsack C. Human Placental Hofbauer Cells Maintain an Anti-inflammatory M2 Phenotype despite the Presence of Gestational Diabetes Mellitus. Front Immunol. 2017 Jul 31;8:888. doi: 10.3389/fimmu.2017.00888. PMID: 28824621; PMCID: PMC5534476.

Schliefsteiner C, Ibesich S, Wadsack C. Placental Hofbauer Cell Polarization Resists Inflammatory Cues In Vitro. Int J Mol Sci. 2020 Jan 22;21(3):736. doi: 10.3390/ijms21030736. PMID: 31979196; PMCID: PMC7038058.

Loegl J, Hiden U, Nussbaumer E, Schliefsteiner C, Cvitic S, Lang I, Wadsack C, Huppertz B, Desoye G. Hofbauer cells of M2a, M2b and M2c polarization may regulate feto-placental angiogenesis. Reproduction. 2016 Nov;152(5):447-55. doi: 10.1530/REP-16-0159. Epub 2016 Aug 17. PMID: 27534571.

Interaction between Macrophages and Endothelial cells – TGFβ signaling and inflammation

Monika Horvat Mercnik - Teammitglied bei PlancentaLab

Monika Horvat Mercnik
PhD Student

Christian Wadsack - Teammitglied bei PlancentaLab

Christian Wadsack
PhD, PI

Triggered by excessive inflammation, endothelial cells might undergo a process called endothelial-to-mesenchymal transition (endoMT) in which endothelial cells lose their typical markers and properties and regress to a mesenchymal phenotype, expressing typical mesenchymal markers. This process is commonly orchestrated by transforming growth factor beta (TGF-β), and related BMP proteins.

Among other cells, macrophages – depending on their polarization state – are a rich source of TGF-β. In this project, we investigate if TGF-β crosstalk between macrophages and endothelial cells in pre-eclampsia, which is an inflammatory disease, alters the capability of placental endothelial cells to maintain their endothelial functions, eventually promoting endoMT. Hence, this study will expand our current knowledge and understanding of placental vascular (dys-)function in health and pre-eclampsia.

Mercnik MH, Schliefsteiner C, Fluhr H, Wadsack C. Placental macrophages present distinct polarization pattern and effector functions depending on clinical onset of preeclampsia. Front Immunol. 2023 Jan 12;13:1095879. doi: 10.3389/fimmu.2022.1095879. PMID: 36713449; PMCID: PMC9878680.

TGFβ signalling: a nexus between inflammation, placental health and preeclampsia throughout pregnancy. Horvat Mercnik M, Schliefsteiner C, Sanchez-Duffhues G, Wadsack C. Hum Reprod Update. 2024 Mar 22:dmae007. doi: 10.1093/humupd/dmae007. Online ahead of print. PMID: 38519450

Small extracellular vesicles in fetal immune communication

Michaela Stoiber - Teammitglied bei PlancentaLab

Michaela Stoiber
MSc

Christian Wadsack
PhD, PI

Extracellular vesicles (EVs) are nano-sized vesicles released by cells that facilitate intercellular communication by transporting proteins, lipids, and nucleic acids. The placenta releases EVs into both maternal and fetal circulation during gestation. While the biological function of placental EVs in the maternal circulation is known, their role in the fetal circulation has not yet been elucidated.

In our project, we aim to understand the function of placental-derived EVs in fetal immune development. Therefore, we are isolating EVs from the conditioned media of primary placental endothelial cells and characterizing their proteomic and miRNA signatures. Furthermore, we are challenging hematopoietic stem and progenitor cells from umbilical cord blood with placental EVs to gain a better understanding in the vesicular-to-cellular communication in the fetal immune development.