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

Hunt Cameron P. J.; Penna Vanessa; Gantner Carlos W.Moriarty NiamhWang YiFranks StephanieErmine Charlotte M.de Luzy Isabelle R.Pavan ChiaraLong Benjamin M.Williams Richard J.Thompson Lachlan H.Nisbet David R.Parish Clare L.

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

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

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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 progenitors by i) including a laminin epitope within the matrix; and ii) shear encapsulating glial cell line-derived neurotrophic factor (GDNF) to ensure its sustained delivery. The biocompatible hydrogel biased a 51% increase in A9 neuron specification-a subpopulation of DA neurons critical for motor function. The sustained delivery of GDNF induced a 2.7-fold increase in DA neurons and enhanced graft plasticity, resulting in significant improvements in motor deficits at 6 months. These findings highlight the therapeutic benefit of stepwise customization of tissue-specific hydrogels to improve the physical and trophic support of human PSC-derived neural transplants, resulting in improved standardization, predictability and functional efficacy of grafts for PD.

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《Advanced functional materials》 |2021年第47期|2105301.1-2105301.17|共17页
作者
Hunt Cameron P. J.; Penna Vanessa; Gantner Carlos W.Moriarty NiamhWang YiFranks StephanieErmine Charlotte M.de Luzy Isabelle R.Pavan ChiaraLong Benjamin M.Williams Richard J.Thompson Lachlan H.Nisbet David R.Parish Clare L.;
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Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3052, Australia;

Australian Natl Univ, Res Sch Chem, Lab Adv Biomat, Canberra, ACT 2601, Australia|Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia;

Federat Univ, Sch Hlth & Life Sci, Mt Helen, Vic 3353, AustraliaDeakin Univ, Sch Med, Ctr Mol & Med Res, Waurn Ponds, Vic 3216, AustraliaAustralian Natl Univ, Res Sch Chem, Lab Adv Biomat, Canberra, ACT 2601, Australia|Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia|Univ Melbourne, Graeme Clark Inst, Fac Engn & Informat Technol, Melbourne, Australia|Univ Melbou;

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正文语种英语
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biomaterials; dopamine; glial cell line-derived neurotrophic factor; hydrogels; laminin; Parkinson's disease; self-assembling peptides; stem cells; transplantation;

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

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