Journal article

Viral Delivery of GDNF Promotes Functional Integration of Human Stem Cell Grafts in Parkinson's Disease

Carlos W Gantner, Isabelle R de Luzy, Jessica A Kauhausen, Niamh Moriarty, Jonathan C Niclis, Christopher R Bye, Vanessa Penna, Cameron PJ Hunt, Charlotte M Ermine, Colin W Pouton, Deniz Kirik, Lachlan H Thompson, Clare L Parish

Cell Stem Cell | CELL PRESS | Published : 2020


Dopaminergic neurons (DAns), generated from human pluripotent stem cells (hPSCs), are capable of functionally integrating following transplantation and have recently advanced to clinical trials for Parkinson's disease (PD). However, pre-clinical studies have highlighted the low proportion of DAns within hPSC-derived grafts and their inferior plasticity compared to fetal tissue. Here, we examined whether delivery of a developmentally critical protein, glial cell line-derived neurotrophic factor (GDNF), could improve graft outcomes. We tracked the response of DAns implanted into either a GDNF-rich environment or after a delay in exposure. Early GDNF promoted survival and plasticity of non-DAns..

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Awarded by NHMRC Australia

Awarded by Swedish Research Council

Funding Acknowledgements

The authors thank Mong Tien and Davor Stanic for expert technical assistance, thank Bjorn Anzelius for production of the AAV vectors, and acknowledge the support of the flow cytometry facility at the Melbourne Brain Centre, Parkville, Australia. C.L.P. was supported by a National Health and Medical Research Council Australia (NHMRC) Senior Research Fellowship. C.W.G. was supported by an Australian Postgraduate Award. This work was supported by an NHMRC Australia project grant (APP1102704 to C.L.P.), Stem Cells Australia (to C.L.P.), and the Swedish Research Council (2012-2586 to D.K.). The Florey Institute of Neuroscience and Mental Health acknowledges the strong support from the Victorian Government and in particular the funding from the Operational Infrastructure Support Grant.