Transplantation of differentiated and genetically modified human embryonic stem cells in Parkinsonian rats via a hydrogel-biomatrix enriched in GDNF, VEGF, reelin and tenascin-C

• Applicant: Gunnar Hargus, Ph.D.
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2008 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 59962383

Parkinson’s disease is associated with a degeneration of dopamine neurons in the substantia nigra causing severe problems in motor initiation and coordination in patients. Since the medical treatment often looses its efficacy over time and may also cause debilitating side effects, this study aims to generate a population of dopaminergic cells derived from human embryonic stem cells that is suitable for replacing degenerated neurons after transplantation. Since the transplantation of highly differentiated and specialized neurons in the brain is known to be associated with problems regarding survival and integration into the host tissue, these cells should be implanted into a rat model of Parkinson’s disease in three-dimensional hydrogel-scaffolds. These scaffolds will contain the growth factors GDNF and VEGF that support cell survival and maintain the dopamine phenotype. Furthermore, these scaffolds will include the matrix proteins reelin and tenascin-C that should mediate cellular integrity due to cell-matrix interaction and should drive the migration of implanted cells inside the host tissue. Additionally, these scaffolds are aimed to attract endogenous, host-derived neuroblasts to support the process of stem cell-mediated regeneration in Parkinsonian rats. Finally, human embryonic stem cells will be genetically modified and FACS-sorted in order to purify the neural cell population and thus to remove residual tumorigenic potential of these cells.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Ole Isacson