Journal article

Tissue Programmed Hydrogels Functionalized with GDNF Improve Human Neural Grafts in Parkinson's Disease

Cameron PJ Hunt, Vanessa Penna, Carlos W Gantner, Niamh Moriarty, Yi Wang, Stephanie Franks, Charlotte M Ermine, Isabelle R de Luzy, Chiara Pavan, Benjamin M Long, Richard J Williams, Lachlan H Thompson, David R Nisbet, Clare L Parish

ADVANCED FUNCTIONAL MATERIALS | WILEY-V C H VERLAG GMBH | Published : 2021

Abstract

The survival and synaptic integration of transplanted dopaminergic (DA) progenitors are essential for ameliorating motor symptoms in Parkinson's disease (PD). Human pluripotent stem cell (hPSC)-derived DA progenitors are, however, exposed to numerous stressors prior to, and during, implantation that result in poor survival. Additionally, hPSC-derived grafts show inferior plasticity compared to fetal tissue grafts. These observations suggest that a more conducive host environment may improve graft outcomes. Here, tissue-specific support to DA progenitor grafts is provided with a fully characterized self-assembling peptide hydrogel. This biomimetic hydrogel matrix is programmed to support DA p..

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Grants

Awarded by NHMRC Dementia Research Leadership Fellowship


Awarded by National Health and Medical Research Council Australia - National Health and Medical Research Council Australia


Awarded by Australian Synchrotron, part of the Australian Nuclear Science and Technology Organisation


Awarded by NSF


Awarded by European Union's Horizon 2020 research and innovation programme under the SINE2020 project


Funding Acknowledgements

C.P.J.H., V.P., and C.W.G. contributed equally to this work. The authors thank Mong Tien and Brianna Xuerub for their expert technical assistance and acknowledge the support of the flow cytometry facility at the Melbourne Brain Centre. V.P. and I.R.d.L. were supported by the University of Melbourne International Scholarships, Australia. C.G. was supported by an Australian Postgraduate Award. D.R.N. was supported by an NHMRC Dementia Research Leadership Fellowship (APP1135687). C.P. was supported by a Senior Research Fellowship provided by the National Health and Medical Research Council Australia. This research was funded by the National Health and Medical Research Council Australia project grants APP11599265 and APP1144996 and 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. Access to the facilities of the Centre for Advanced Microscopy (CAM) with funding through the Australian Microscopy and Microanalysis Research Facility (AMMRF) is gratefully acknowledged. This research was undertaken on the small angle X-ray scattering beamline at the Australian Synchrotron, part of the Australian Nuclear Science and Technology Organisation (Application AS193/SAXS/15472). This work benefited from the use of the SasView application, originally developed under NSF award DMR0520547. SasView contains code developed with funding from the European Union's Horizon 2020 research and innovation programme under the SINE2020 project, grant agreement no. 654000.