Article

Stem Cell Reviews and Reports

, Volume 10, Issue 2, pp 251-268

First online:

Neuroprotective Effects of GDNF-expressing Human Amniotic Fluid Cells

  • Anna JezierskiAffiliated withDepartment of Translational Biosciences, National Research Council CanadaDepartment of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa
  • , Kerry RennieAffiliated withDepartment of Translational Biosciences, National Research Council Canada
  • , Bogdan ZurakowskiAffiliated withDepartment of Translational Biosciences, National Research Council Canada
  • , Maria Ribecco-LutkiewiczAffiliated withDepartment of Translational Biosciences, National Research Council Canada
  • , Julie HaukenfrersAffiliated withDepartment of Translational Biosciences, National Research Council Canada
  • , Abdellah AjjiAffiliated withDepartment of Chemical Engineering, Polytechnique Montréal
  • , Andrée GruslinAffiliated withDepartment of Cellular and Molecular Medicine, Faculty of Medicine, University of OttawaDepartment of Obstetrics and Gynecology, Faculty of Medicine, University of Ottawa
  • , Marianna SikorskaAffiliated withDepartment of Translational Biosciences, National Research Council Canada
  • , Mahmud Bani-YaghoubAffiliated withDepartment of Translational Biosciences, National Research Council CanadaDepartment of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa Email author 

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Abstract

Brain injury continues to be one of the leading causes of disability worldwide. Despite decades of research, there is currently no pharmacologically effective treatment for preventing neuronal loss and repairing the brain. As a result, novel therapeutic approaches, such as cell-based therapies, are being actively pursued to repair tissue damage and restore neurological function after injury. In this study, we examined the neuroprotective potential of amniotic fluid (AF) single cell clones, engineered to secrete glial cell derived neurotrophic factor (AF-GDNF), both in vitro and in a surgically induced model of brain injury. Our results show that pre-treatment with GDNF significantly increases cell survival in cultures of AF cells or cortical neurons exposed to hydrogen peroxide. Since improving the efficacy of cell transplantation depends on enhanced graft cell survival, we investigated whether AF-GDNF cells seeded on polyglycolic acid (PGA) scaffolds could enhance graft survival following implantation into the lesion cavity. Encouragingly, the AF-GDNF cells survived longer than control AF cells in serum-free conditions and continued to secrete GDNF both in vitro and following implantation into the injured motor cortex. AF-GDNF implantation in the acute period following injury was sufficient to activate the MAPK/ERK signaling pathway in host neural cells in the peri-lesion area, potentially boosting endogenous neuroprotective pathways. These results were complemented with promising trends in beam walk tasks in AF-GDNF/PGA animals during the 7 day timeframe. Further investigation is required to determine whether significant behavioural improvement can be achieved at a longer timeframe.

Keywords

Amniotic fluid cells Brain injury GDNF Neuroprotection Polyglycolic acid Stem cells