Regenerative potential of combined administration of iPS cell-derived neural progenitor cells and neuroprotective compounds in a rat model of focal traumatic brain injury

• Applicants: Professor Dr. Edmund A. M. Neugebauer; Dr. Tomo Saric
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Clinical Neurology; Neurosurgery and Neuroradiology ; Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 261920491

Traumatic brain injury (TBI) is the leading cause of death and disability worldwide, thus representing a highly relevant medical and socio-economic problem. Transplantation of pluripotent stem cell derivatives holds great potential for the treatment of TBI. We hypothesize that transplantation of induced pluripotent stem cell-derived neural progenitor cells (iPS-NPCs) may improve the functional outcome after TBI and that the systemic co-administration of proneurogenic and neuroprotective compounds to animals with TBI can enhance their survival, engraftment, therapeutic efficacy and safety. After lateral fluid percussion focal brain injury the immunosuppressed rats will receive one stereotactic injection of human eGFP- and luciferase-expressing iPSC-NPCs with or without the compound found to have the best protective activity on iPSC-NPCs in toxicity assays in vitro. Utilizing the most effective cell dose and the best time point of transplantation after TBI the functional benefit of transplanted NPCs will be assessed using an array of neurobehavioral tests. The cell survival will be monitored by in vivo bioluminescence imaging and immunohistological analyses will be employed to determine the location, engraftment, migration, short-term safety and connectivity of transplanted with endogenous cells. These analyses will increase our understanding of the therapeutic potential of human iPSC-NPCs in combination with neuroprotective compounds and provide a basis for future follow-up studies in which the long-term safety and efficacy of this new therapeutic concept, exact mechanism of its therapeutic action, types of interactions of transplanted cells with the recipient cells can be further explored with the ultimate aim to translate iPSC-based concepts into human therapy.

• DFG Programme: Research Grants
• International Connection: Austria
• Participating Person: Professorin Ute Schäfer, Ph.D.