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Literature DB >> 27133795

Chemical Control of Grafted Human PSC-Derived Neurons in a Mouse Model of Parkinson's Disease.

Yuejun Chen¹, Man Xiong², Yi Dong³, Alexander Haberman³, Jingyuan Cao³, Huisheng Liu³, Wenhao Zhou², Su-Chun Zhang⁴.

Abstract

Transplantation of human pluripotent stem cell (hPSC)-derived neurons is a promising avenue for treating disorders including Parkinson's disease (PD). Precise control over engrafted cell activity is highly desired, as cells do not always integrate properly into host circuitry and can cause suboptimal graft function or undesired outcomes. Here, we show tunable rescue of motor function in a mouse model of PD, following transplantation of human midbrain dopaminergic (mDA) neurons differentiated from hPSCs engineered to express DREADDs (designer receptors exclusively activated by designer drug). Administering clozapine-N-oxide (CNO) enabled precise DREADD-dependent stimulation or inhibition of engrafted neurons, revealing D1 receptor-dependent regulation of host neuronal circuitry by engrafted cells. Transplanted cells rescued motor defects, which could be reversed or enhanced by CNO-based control of graft function, and activating engrafted cells drives behavioral changes in transplanted mice. These results highlight the ability to exogenously and noninvasively control and refine therapeutic outcomes following cell transplantation.

Entities: CellLine Chemical Disease Gene Mutation Species

Mesh：

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Year: 2016 PMID： 27133795 PMCID： PMC4892985 DOI： 10.1016/j.stem.2016.03.014

Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633

33 in total

1. Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand.

Authors: Blaine N Armbruster; Xiang Li; Mark H Pausch; Stefan Herlitze; Bryan L Roth
Journal: Proc Natl Acad Sci U S A Date: 2007-03-02 Impact factor: 11.205

2. An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology.

Authors: Alexander M Aravanis; Li-Ping Wang; Feng Zhang; Leslie A Meltzer; Murtaza Z Mogri; M Bret Schneider; Karl Deisseroth
Journal: J Neural Eng Date: 2007-05-31 Impact factor: 5.379

3. Generation of regionally specified neural progenitors and functional neurons from human embryonic stem cells under defined conditions.

Authors: Agnete Kirkeby; Shane Grealish; Daniel A Wolf; Jenny Nelander; James Wood; Martin Lundblad; Olle Lindvall; Malin Parmar
Journal: Cell Rep Date: 2012-05-26 Impact factor: 9.423

4. Transplantation of embryonic dopamine neurons for severe Parkinson's disease.

Authors: C R Freed; P E Greene; R E Breeze; W Y Tsai; W DuMouchel; R Kao; S Dillon; H Winfield; S Culver; J Q Trojanowski; D Eidelberg; S Fahn
Journal: N Engl J Med Date: 2001-03-08 Impact factor: 91.245

Review 5. Chemogenetic tools to interrogate brain functions.

Authors: Scott M Sternson; Bryan L Roth
Journal: Annu Rev Neurosci Date: 2014-06-16 Impact factor: 12.449

Review 6. L-DOPA and graft-induced dyskinesia: different treatment, same story?

Authors: Ludivine S Breger; Emma L Lane
Journal: Exp Biol Med (Maywood) Date: 2013-07-04

7. Remote control of neuronal activity in transgenic mice expressing evolved G protein-coupled receptors.

Authors: Georgia M Alexander; Sarah C Rogan; Atheir I Abbas; Blaine N Armbruster; Ying Pei; John A Allen; Randal J Nonneman; John Hartmann; Sheryl S Moy; Miguel A Nicolelis; James O McNamara; Bryan L Roth
Journal: Neuron Date: 2009-07-16 Impact factor: 17.173

Review 8. Dopaminergic modulation of synaptic transmission in cortex and striatum.

Authors: Nicolas X Tritsch; Bernardo L Sabatini
Journal: Neuron Date: 2012-10-04 Impact factor: 17.173

9. Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's disease.

Authors: Sonja Kriks; Jae-Won Shim; Jinghua Piao; Yosif M Ganat; Dustin R Wakeman; Zhong Xie; Luis Carrillo-Reid; Gordon Auyeung; Chris Antonacci; Amanda Buch; Lichuan Yang; M Flint Beal; D James Surmeier; Jeffrey H Kordower; Viviane Tabar; Lorenz Studer
Journal: Nature Date: 2011-11-06 Impact factor: 49.962

10. Human ESC-derived dopamine neurons show similar preclinical efficacy and potency to fetal neurons when grafted in a rat model of Parkinson's disease.

Authors: Shane Grealish; Elsa Diguet; Agnete Kirkeby; Bengt Mattsson; Andreas Heuer; Yann Bramoulle; Nadja Van Camp; Anselme L Perrier; Philippe Hantraye; Anders Björklund; Malin Parmar
Journal: Cell Stem Cell Date: 2014-11-06 Impact factor: 24.633

58 in total

Review 10. Therapeutic potential of combined viral transduction and CRISPR/Cas9 gene editing in treating neurodegenerative diseases.

Authors: Joshua Kuruvilla; Andrew Octavian Sasmita; Anna Pick Kiong Ling
Journal: Neurol Sci Date: 2018-08-03 Impact factor: 3.307

Chemical Control of Grafted Human PSC-Derived Neurons in a Mouse Model of Parkinson's Disease.

1. Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand.

2. An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology.

3. Generation of regionally specified neural progenitors and functional neurons from human embryonic stem cells under defined conditions.

4. Transplantation of embryonic dopamine neurons for severe Parkinson's disease.

Review 5. Chemogenetic tools to interrogate brain functions.

Review 6. L-DOPA and graft-induced dyskinesia: different treatment, same story?

7. Remote control of neuronal activity in transgenic mice expressing evolved G protein-coupled receptors.

Review 8. Dopaminergic modulation of synaptic transmission in cortex and striatum.

9. Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's disease.

10. Human ESC-derived dopamine neurons show similar preclinical efficacy and potency to fetal neurons when grafted in a rat model of Parkinson's disease.

Review 1. Pluripotent stem cell-based therapy for Parkinson's disease: Current status and future prospects.

Review 2. Quantitative Rodent Brain Receptor Imaging.

3. In Vivo Chimeric Alzheimer's Disease Modeling of Apolipoprotein E4 Toxicity in Human Neurons.

Review 4. Next-generation stem cells - ushering in a new era of cell-based therapies.

5. Using Induced Pluripotent Stem Cells to Investigate Complex Genetic Psychiatric Disorders.

Review 6. Neural Subtype Specification from Human Pluripotent Stem Cells.

Review 7. Reprogramming Glial Cells into Functional Neurons for Neuro-regeneration: Challenges and Promise.

8. CNO Evil? Considerations for the Use of DREADDs in Behavioral Neuroscience.

Review 9. Cell replacement therapy is the remedial solution for treating Parkinson's disease.

Review 10. Therapeutic potential of combined viral transduction and CRISPR/Cas9 gene editing in treating neurodegenerative diseases.