Molecular Biotechnology and Stem Cell Research

Stem cells are non- or only partially specialized cells which have the potential to differentiate into multiple cell types and can theoretically be expanded indefinitely. Adult stem cells are found in many organs and differentiated tissues and are indispensible for continuous tissue regeneration and wound healing. However, adult stem cells have a limited capacity for self renewal and differentiation, restricting their application in cell-based therapies.

 

In contrast, embryonic stem (ES) cells not only exhibit an unlimited proliferation potential, but can develop in the embryo into all cell types of the human body including cardiomyocytes and airway-specific cells. For these reasons, ES cells, at least in theory, represent an excellent cell source for novel approaches in regenerative medicine. However, these cells are usually not autologous, i.e. they differ genetically from the recipient and, like transplanted organs, can thus provoke immunological tissue rejection. Additionally, the use of ES cells remains ethically controversial as obtaining the cells necessitates the destruction of the embryo.

 

In 2006, S. Yamanaka described so-called induced pluripotent stem (iPS) cells for the first time. These cells closely resemble ES cells in their properties and functionality and they also show an unlimited proliferation potential and can be differentiated into multiple cell types. In contrast to ES cells, iPS cells are generated by the in vitro reprogramming of adult somatic cells which entails altering the gene expression profile by means of additive gene transfer via so-called pluripotency factors. Through overexpression of a defined set of transcription factors, the cell can be “reset” to a pluripotent state. Hence, reprogramming avoids the ethical concerns associated with ES cells, and also offers the opportunity to create patient- or disease-specific stem cell lines. These not only represent novel tools for studying genetic diseases or drug screening but can also help to generate patient-specific cell lines in amounts sufficient for cell therapeutic approaches. However, potential risks such as teratoma formation based on chromosomal abnormalities remain and need to be extensively characterized and minimized prior to beginning clinical trials.

In the research area Molecular Biotechnology and Stem Cell Research at the LEBAO, we focus on the following priorities: the detailed evaluation of the molecular mechanisms underlying reprogramming, genetic modification of iPS cells, differentiation of stem and progenitor cells into cardiomyocytes, airway epithelial cells and endothelial cells, and the mass production of differentiated cells.

 

The groundwork for the development of novel cell-based therapies for the treatment of cardiac and pulmonary diseases is laid through investigations on a molecular and cellular level. Thereby, our research not only focuses on adult resident stem cells and ES cells, but also on iPS cells as an emerging tool for disease modeling, drug screening and patient-specific therapies.

 

ES and iPS cell-derived cardiomyocytes are used for the production of bioartificial heart muscle whereas other projects aim at the development of a stem cell-based biological cardiac pacemaker or the cellular treatment of genetic lung diseases. In addition, the establishment of efficient and cell type-specific gene transfer methods, in particular for application in different stem cell types, are key technologies in this research area.