Stem Cell-based Disease Modeling and Regenerative Therapies

Our research aims to elucidate the potential of stem cells, especially induced pluripotent stem cells (iPSCs), for the use in regenerative medicine and for modeling human diseases.

iPSCs are generated by reprogramming somatic cells to an embryonic stem cell-like state via ectopic expression of a distinct transcription factor cocktail. Due to their pluripotent nature, iPSCs can be differentiated into many cell types. The use of iPSCs offers the possibility for personalized regenerative therapies with autologous or allogenic cells or tissue as well as in vitro disease modeling in human cells. 

Currently, we are modeling sporadic Alzheimer’s disease (SAD), which is the most common age-related dementia. Using either SAD patient-derived iPSCs or isogenic cells that differ only in their SAD risk genes, we analyze disease-relevant pathomechanisms in differentiated cortical neurons and astrocytes.
In another project, we focus on improving cell-based, regenerative therapies for stroke and cardiac infarction.

Methods:

induced pluripotent stem cells (iPSCs), neural progenitor cells (NPCs), human induced neurons, human astrocytes, 3D cell culture, viral transduction, protein biochemistry, molecular and cell biological techniques, confocal imaging

Human EGFP expressing iN cells in culture
Characterization of human iPSCs and induced neuronal (iN) cells. A: Representative images of one HCS- and one AD patient-derived iPS cell line. IPSCs but not fibroblasts showed an embryonic stem cell-like morphology and expressed the pluripotency markers Nanog (red) and Tra-1-60 (green). Scale bar: 300 μm. B: Induced neurons at day 21 after differentiation stained positive for the neuronal marker Map2 (red) and the presynaptic marker synapsin (green). Scale bar: 200 μm (top), 25 μm (bottom). Modified from Birnbaum et al., 2018, Stem Cell Research

Funding:

Swiss Commission for Technology and Innovation (CTI); Novartis Foundation for medical-biological research; University of Zurich; Olga Mayenfisch Foundation