• BCRT

Cellular Programming

Daniel Ortmann

We aim to generate commercially and therapeutically relevant human cells with enhanced functionality by means of cellular programming. We develop novel ways to control cells by identifying the key factors that determine cellular identity. Then, we engineer instructive cues that guide the cells towards the desired phenotype and function.

Prof. Dr. Daniel Ortmann

E-mail:
daniel.ortmann[at]bih-charite.de
Address:
Berlin Institute of Health
Center for Regenerative Therapies
Föhrer Straße 15
13353 Berlin

Stem cells and regenerative therapies

Pluripotent Stem Cells (PSCs) hold enormous potential as they can be differentiated into any human cell type. This makes them invaluable for studying diseases and developing new regenerative therapies, especially for cell types that are hard to obtain from other sources. However, we have not yet fully realized the potential of PSCs. One major challenge is that differentiating them into the right cell type in the lab is a very complex and lengthy process. The traditional method tries to imitate the natural developmental signals, but our understanding is still incomplete, and some cell types take several months to differentiate this way. Even if we manage to obtain the desired cell type this way, the usually lack maturity and functionality in comparison with the primary cells in the human body, which severly limits their utility.

Cell engineering and programming

In the search for a better way to control cell identity, researchers have expressed certain “master transcription factors”. These factors regulate many other genes, triggering a cascade of events that reprograms a cell into a new type. Pioneering work in this area includes Weintraub and Lassar's use of Myod1 to convert fibroblasts into skeletal muscle, and Takahashi and Yamanaka's use of four factors to create induced Pluripotent Stem Cells (iPSCs) from fibroblasts.

We now use improved, controllable methods to express various combinations of these master transcription factors. This allows us to program iPSCs into a range of valuable cell types, including glutamatergic neurons, skeletal myocytes, oligodendrocytes, and hepatocytes.

Integrating the master transcription factors into so called genetic safe harbour ensures that these genetic modifications are safe and clinically compatible and that every cell gets the same amount of signal leading to increased reproducibility. Using iPSCs as a starting cell type we can generate a virtually unlimited supply of cells resulting in a system that shows superior performance in terms of consistency, efficacy and scalability.

Environment and epigenetics

While this cell programming technique is powerful, many other factors influence a cell's identity. These include the signalling environment, cellular metabolism, the extracellular matrix, epigenetic status, and genetic mutations. By investigating these influences, we can ensure that our cells receive all the correct signals while avoiding detrimental ones. This will enable us to precisely control cell identity and maximize their functionality for specific applications. Taking all these aspects together, we aim to develop safer and more effective cell therapies.

Selected publications

Links