Journal article

Human stem cells harboring a suicide gene improve the safety and standardisation of neural transplants in Parkinsonian rats

Isabelle R de Luzy, Kevin CL Law, Niamh Moriarty, Cameron PJ Hunt, Jennifer C Durnall, Lachlan H Thompson, Andras Nagy, Clare L Parish

NATURE COMMUNICATIONS | NATURE RESEARCH | Published : 2021

Abstract

Despite advancements in human pluripotent stem cells (hPSCs) differentiation protocols to generate appropriate neuronal progenitors suitable for transplantation in Parkinson's disease, resultant grafts contain low proportions of dopamine neurons. Added to this is the tumorigenic risk associated with the potential presence of incompletely patterned, proliferative cells within grafts. Here, we utilised a hPSC line carrying a FailSafeTM suicide gene (thymidine kinase linked to cyclinD1) to selectively ablate proliferative cells in order to improve safety and purity of neural transplantation in a Parkinsonian model. The engineered FailSafeTM hPSCs demonstrated robust ventral midbrain specificati..

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Grants

Funding Acknowledgements

The authors thank Mong Tien and Brianna Xuereb for their expert technical assistance. We would also like to thank Natalie Payne and Katherine Davidson for their invaluable guidance. I.D.L. was supported by The University of Melbourne International Scholarships, Australia. C.P. was supported by a Senior Research Fellowship provided by the National Health and Medical Research Council Australia. This research was funded by Stem Cells Australia. 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. The Australian Institute of Regenerative Medicine (ARMI) is supported by grants from the State government of Victoria and the Australian government.