Differentation, Subgroup Biochemistry

Objectives

The Junior Research Group 'Differentiation' aims at the in vitro generation of surrogate somatic cells from embryonic stem cells for cell replacement therapy of human diseases. The group is allocated to two departments, the Inst. of Clinical Biochemistry (Head: Prof. S. Lenzen) and the Dept. of Experimental Hematology (Head: Prof. C. Baum) and focuses on the generation of two main types of cells: The group of Prof. Lenzen´s department focuses on the differentiation of mouse and human ES cells into insulin-producing cells with similar characteristics of pancreatic beta cells as a potential cell source for treatment of Diabetes mellitus. The group at Prof. Baum´s department focuses on the generation of transplantable hematopoietic (i.e. blood-producing) stem cells from pluripotent ES- and iPS cells, in vitro.

Research Focus

The main aim of our studies is to generate insulin-secreting surrogate cells from mouse and human embryonic stem cells (ES cells) suitable for insulin replacement therapy of patients with Type 1 diabetes in order to cure insulin deficiency. In recent years we have developed sophisticated new in vitro methods for differentiation of ES cells towards insulin-producing cells. Implantation of differentiated ES cells from our differentiation protocol prevented the rise of blood glucose in STZ diabetic mice, and caused a significant reduction of blood glucose concentrations towards a range typical for non-diabetic mice. Additionally, implantation of ES cells differentiated in vitro into insulinproducing cells (according to our differentiation protocol) showed a further beneficial effect owing to final maturation in the in vivo environment. In order to avoid teratoma formation and to minimize cellular over-proliferation, we have established a suicide gene expression system (Oct4- HSVtk), which allows metabolic selection against remaining undifferentiated ES cells without harming other nonembryonic cell types. Our protocols will also be tested in human ES cell lines, for which we have obtained a license for import under the recently changed German Stem Cell Law.

Collaborations

  • Prof. R. Gerardy-Schahn, Dr. H. Bakker, Hannover Medical School, REBIRTH Unit Stem Cell Glycomics and Proteomics, Analysis of changes in the glycom of undifferentiated and differentiated ES cells
  • Prof. C. J. Bailey, Aston University Birmingham, Department of Pharmaceutical Sciences, Cooperation on implantation and in vivo function of transplanted insulin-producing cells differentiated from stem cells
  • Prof. P. M. Jones, GKT School of Biomedical Sciences, King’s College London, Division of Reproduction and Endocrinology, Cooperation on cultivation and differentiation of human ES cells

Awards

  • Dr. O. Naujok has been awarded the Junior Award of the German Diabetes Association (2009)
  • Prof. C. Baum has been awarded the animal protection award (The Ursula M. Händel animal welfare Prize) of the DFG (2009)

Equipment and Service Facilities

[Please find a list of all available equipment here]

Publications

[Please find the publications of this workgroup here]

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