Human Embryonic Stem Cells in Animal Models of Neurodegenerative Diseases: The Role of Inflammation

Principal Investigators: OUTI HOVATTA1, JARI KOISTINAHO2, SEPPO YLÄ-HERTTUALA2

 1Department of Regenerative Medicine REGEA, University of Tampere, Finland, 2A.I. Virtanen Institute, University of Kuopio, Finland

The project is carried out in a consortium of three expert groups representing completely different but complementary and synergistic fields of biosciences. The team in REGEA, Outi Hovatta as the PI, has extensive experience from derivation and differentiation of hESC. Jari Koistinaho's team in the A.I. Virtanen institute in Kuopio has expertise in animal models and cell transplantation of degenerative neurological diseases, and methods to analyse the biological events in cell survival, migration and function. Seppo Ylä-Herttuala's team in A.I. Virtanen Institute has unique competence in gene transfer. 

Human embryonic stem cells (hESC) are pluripotent cells, which can be obtained from the inner cell mass of human embryos 5-6 days after in vitro fertilisation. They grow as permanent lines, which can be propagated, in large amounts. They are an excellent source of stem cells for potential treatment of severe disorders, including neurodegenerative diseases. Using culture media optimized for neural differentiation in a sequential manner, we can differentiate hESC to neural progenitors and then through all the developmental stages to mature neurons and glia cells, of both in central and peripheral nervous systems. The culture media are serum-free and they contain several growth factors known to induce neural differentiation in vivo. The development in vitro follows the order and time schedule as in the embryo in vivo. We are differentiating hESC to neural progenitor cells and more mature cells of the neural tissue. The function of these cells in then studied in animal models for stroke, ALS and spinal cord injury with the other teams of the consortium. The optimal differentiation stage before transplantation will be studied, as well as the role of inflammation in the survival and migration of the cells. We are also going to study if increasing the blood circulation using gene transfer of vascular growth factors promotes the function of the transplants.

Contact: outi.hovatta(at)klinvet.ki.se, tel. +358 3 215 8495