KB01

3D vascularized human adipose tissue model containing immune cells for disease modeling

Supervisors

Karen Bieback, Heidelberg University
Rüdiger Rudolf, Mannheim University for Applied Sciences

Project description

Our group has extensive knowledge on adipose-derived stromal cells for cell-based therapies [1, 2]. Extending on this expertise, the aim of this project is to develop a physiological in vitro 3-dimensional (3D) vascularized human adipose tissue model containing immune cells as a tool for (immune) disease modeling. Increasing data indicate that multiple changes in the innate immune system are key contributors to inflammation in obese adipose tissue. Based on cells isolated from the adipose tissue stromal vascular fraction, spheroids, organoids and bioprinted 3D constructs will be established capable of maintaining adipose-resident immune cell subsets. A specific focus will be on enabling the model to study the specific contribution of innate immune cells, e.g. regulatory T cells, innate lymphoid cells and macrophages and to use this to establish novel therapeutic interventions.

Live-cell imaging, next to high-content imaging will be applied to monitor cell growth, cell-and cell interactions. Metabolic and inflammatory activity will be monitored by multiplex cytokine analyses, lipidomics/metabolomics upon anti-angiogenic, immunomodulatory or dietary interventions.

References

1. Fiori A, Uhlig S, Klüter H, Bieback K. Human Adipose Tissue-Derived Mesenchymal Stromal Cells Inhibit CD4+ T Cell Proliferation and Induce Regulatory T Cells as Well as CD127 Expression on CD4+CD25+ T Cells.Cells. 2021;10(1):58. doi: 10.3390/cells10010058
2. Fiori A, Hammes HP, Bieback K. Adipose-derived mesenchymal stromal cells reverse high glucose-induced reduction of angiogenesis in human retinal microvascular endothelial cells. Cytotherapy. 2020;22(5):261-275. doi: 10.1016/j.jcyt.2020.02.005.
3. Bieback K, Hecker A, Schlechter T, Hofmann I, Brousos N, Redmer T, Besser D, Klüter H, Müller AM, Becker M. Replicative aging and differentiation potential of human adipose tissue-derived mesenchymal stromal cells expanded in pooled human or fetal bovine serum. Cytotherapy. 2012;14(5):570-83. doi: 10.3109/14653249.2011.652809

Methods used

Primary cell culture, 3D cell culture, bioprinting, flow cytometry, 2D/3D and live cell imaging, optical tissue clearing, AI-assisted image analysis, multiplex analysis, single cell analyses, lipidomis/metabolomics

Collaboration Partner

• Prof. Dr. Rüdiger Rudolf (image analysis),
• Prof. Dr. Nicole Rotter (3D models, bioprinting),
• Dr. Christoph Köpple, BGU Ludwigshafen (patient material, disease modeling)

Applicants profile

The successful candidate holds a Master degree in biosciences, biotechnology, or similar and has a strong interest in cell biology and immunology. Sound work ethics and the will to drive the project in a cooperative team effort are mandatory. Experience with adipose tissue, stem/stromal, endothelial and immune cell culture in 2D and 3D, flow cytometry, confocal microscopy, advanced image analysis, and a propensity for technological solutions, including 3D-(bio) printing are an asset.