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Publications
- Mai, Patrick, Jörg Hampl, Martin Baca, Dana Brauer, Sukhdeep Singh, Frank Weise, Justyna Borowiec, André Schmidt, Johanna Merle Küstner, Maren Klett, Michael Gebinoga, Insa S. Schroeder, Udo R. Markert, Felix Glahn, Berit Schumann, Diana Eckstein, and Andreas Schober. 2022. "MatriGrid® Based Biological Morphologies: Tools for 3D Cell Culturing" Bioengineering 9, no. 5: 220.
- Schmidt A, Schmidt A, Markert UR. The road (not) taken – Placental transfer and interspecies differences. Placenta 115, Nov 2021, Pages 70-77.
- Fuentes-Zacarías P, Murrieta-Coxca JM, Gutierrez-Samudio RN, Schmidt A, Schmidt A, Markert UR, Morales-Prieto DM: Pregnancy and pandemics: Interaction of viral surface proteins and placenta cells. BBA - Molecular Basis of Disease 2021.
- Heger J, Froehlich K, Pastuschek J, Schmidt A, Baer C, Mrowka R, Backsch C, Schleußner E, Markert UR, Schmidt A, 2018. Human serum alters cell culture behavior and improves spheroid formation in comparison to fetal bovine serum. Exp Cell Res, 365(1):57-65.
- Karolin Fröhlich, Julia I. Heger, Andre Schmidt, Astrid Schmidt, Yvonne Heimann, Amelie Lupp, Rikst Nynke Verkaik-Schakel, Gitta Turowski, Sibylle Loibl, Torsten Plosch, Udo R. Markert, 2018. Effects of breast cancer treatment on placental tissue. Poster and abstract, IFPA 2018 Tokyo conference (International Federation of Placenta Associations).
Current projects André Schmidt
Platox (BMBF 2021-2024)
cand. Dr. med. dent.: Enora Flache
Masterstudentinnen: Katherine Phillips
The PlaTox project (Placenta Toxicology - human placenta explants for drug testing) is a cooperation with the Department of Nanobiosystem Technology at the TU Ilmenau and is funded within the BMBF programme "Validation of the technological and societal innovation potential of scientific research - VIP+". The bilateral cooperation project led by Prof. Andreas Schober of the TU Ilmenau and Prof. Udo Markert of the Placenta Laboratory could be started on March 15, 2021 and will run for 3 years. Dr. André Schmidt and Dr. Astrid Schmidt from the Placenta-Laboratory are responsible for the implementation of the project in Jena. PlaTox is intended to contribute to reducing animal experiments in toxicology and to increasing the relevance of toxicological investigations by using vital human tissue.
In PlaTox, a system will be developed in which placental explants will be routinely used for reproductive toxicology as well as general toxicology studies. The placental explant model is a heterocellular, primary, human tissue model that more realistically represents the in vivo situation than cell lines or even cell line-based 3D co-culture systems. The explants provide a physiological, heterocellular tissue composite of primary, human material that is available in sufficient quantity to enable inexpensive mass screening if the project is successful.
In PlaTox, an automated system will be developed and used to generate large numbers of placental explants, which will then be incubated with test substances in microculture flow chamber systems in microtiter plate format for at least two weeks. The system should allow regular or permanent measurement of numerous parameters.
Toxicological studies on human placenta will be used as a crucial step prior to clinical trials and will help to estimate and test the transferability of preclinical results to humans.
PlaTox could support toxicological as well as pharmacological studies according to the German Drug Law or Medical Device Law (AMG/MPG). It is planned to offer the test systems under development to clinical research groups as well as companies for use.
The approved funding amounts to approx. 1.8 million €, of which 685,446 € will go to the Placenta Laboratory.
Members
Alumni
- Sarah Avemarg, Dr. med. Evaluierung der Bestimmung von Biomarkern für toxikologische Tests an der menschlichen Plazenta, 2021.
- Nora Schulz, M.Sc. Optimierung der 14-tägigen Kultivierung von humanen Plazenta‑Explantaten mit anschließendem Toxizitäts-Assay (Master thesis, 2019)
Current projects Astrid Schmidt
Optobiopsy (ZIM/ BMWi 2022-2025)
Senescence in humane placenta explants (IZKF (2023)
Senescence in the humane endometrium (JSAM 2021-2023)
Multiplex analysis of human placenta explants in heavy metal toxicity
Master student: Karthika Muthuraj
Multiplex analysis of human placenta explants after long-term culture in different heavy metals.
Members
In vitro-toxicology
Before chemicals and pharmaceuticals can enter the market they have to be tested for potential adverse effects on human health. Usually, such investigations are performed using mice and rats, but also other animal species are used in toxicity testing, e.g., dogs and primates. Apart from ethical concerns animal experiments are characterized by problems with regard do the limited predicitvity for human biology. Prominent examples are thalidomide and the monoclonal antibody TGN1412 which passed toxicity testing in animals but led to serious adverse effects in humans. Therefore, an urgent need for new approaches on the basis of human cells and tissues, representing human biology better than animal models, is existing in toxicology.
The placenta in toxicology
The placenta is a complex organ which is responsible for the feto-maternal exchange, but also plays a central role in the maintenance of pregnancy or protecting the fetus against the maternal immune system. In addition to placenta-specific trophoblasts with importance for substance transfer across the placental barrier, the placenta contains a range of further cell types, for example different kinds of immune cells, fibroblasts, stem cells or endothelial cells.
At the same time, the placenta is the only organ of humans which is permanently available for research in a healthy condition. The complexity in combination with the fact that the placenta or tissue explants stay vital for a longer period of time after delivery, makes it a perfect model for human toxicity testing. Apart from the field of general toxicity testing the placenta, amongst others, can be used for immunotoxicity, reproductive toxicity, the analysis of substances affecting the hormone system and toxic effects or transfer of nanoparticles.
In contrast to other in-vitro-models the placenta combines the following advantages
- all cells are primary cells of human origin
- all cells are located in their natural environment, important for cell-cell-interactions (e.g., between immune cells and endothelial cells)
- the placenta is permanently available
- the placenta is a healthy organ which is not coined by pathological processes which could influence the experimental results in toxicity testing
- numerous parameters can be measured at the same time point, for example cytokine release of immune cells and hormone production of trophoblasts
- placental tissue explants can be cultivated with autologues blood which could be of significance when substances are bound to serum proteins
The toxicological placenta cascade
The placenta offers the opportunity to analyze chemicals and pharmaceuticals in a cascade of increasing complexity. The first steps of the cascade are characterized by low costs and and time consumption and can be used for identifying toxic substances early. The later steps are more complex and serve the toxicological analysis of substances which passed the first steps without obvious toxic effects.
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Reference:
Scanning Electron Microscopy Images: Sandor Nietzsche, Center for Electron Microscopy, Jena University Hospital