Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease
Sonja Kriks,Jae-Won Shim,Jinghua Piao,Yosif Ganat,Dustin R. Wakeman,Zhi-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 +15 more
TLDR
A novel floor-plate-based strategy for the derivation of human DA neurons that efficiently engraft in vivo is presented, suggesting that past failures were due to incomplete specification rather than a specific vulnerability of the cells.Abstract:
Human pluripotent stem cells (PSCs) are a promising source of cells for applications in regenerative medicine. Directed differentiation of PSCs into specialized cells such as spinal motoneurons or midbrain dopamine (DA) neurons has been achieved. However, the effective use of PSCs for cell therapy has lagged behind. Whereas mouse PSC-derived DA neurons have shown efficacy in models of Parkinson's disease, DA neurons from human PSCs generally show poor in vivo performance. There are also considerable safety concerns for PSCs related to their potential for teratoma formation or neural overgrowth. Here we present a novel floor-plate-based strategy for the derivation of human DA neurons that efficiently engraft in vivo, suggesting that past failures were due to incomplete specification rather than a specific vulnerability of the cells. Midbrain floor-plate precursors are derived from PSCs 11 days after exposure to small molecule activators of sonic hedgehog (SHH) and canonical WNT signalling. Engraftable midbrain DA neurons are obtained by day 25 and can be maintained in vitro for several months. Extensive molecular profiling, biochemical and electrophysiological data define developmental progression and confirm identity of PSC-derived midbrain DA neurons. In vivo survival and function is demonstrated in Parkinson's disease models using three host species. Long-term engraftment in 6-hydroxy-dopamine-lesioned mice and rats demonstrates robust survival of midbrain DA neurons derived from human embryonic stem (ES) cells, complete restoration of amphetamine-induced rotation behaviour and improvements in tests of forelimb use and akinesia. Finally, scalability is demonstrated by transplantation into parkinsonian monkeys. Excellent DA neuron survival, function and lack of neural overgrowth in the three animal models indicate promise for the development of cell-based therapies in Parkinson's disease.read more
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Targeted Differentiation of Regional Ventral Neuroprogenitors and Related Neuronal Subtypes from Human Pluripotent Stem Cells
Liankai Chi,Beibei Fan,Kunshan Zhang,Yanhua Du,Zhongliang Liu,Yujiang Fang,Zhenyu Chen,Xudong Ren,Xiangjie Xu,Cizhong Jiang,Siguang Li,Lin Ma,Liang Gao,Ling Liu,Xiaoqing Zhang +14 more
TL;DR: Embryoid body (EB) formation and adherent culture (AD) paradigms are equivalently thought to be applicable for neural specification of human pluripotent stem cells and can be integrated together to specify distinct neuronal subtypes for studying and treating related neurological diseases, such as epilepsy, Alzheimer's disease, and Parkinson's disease.
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Atypical neurogenesis in induced pluripotent stem cell (iPSC) from autistic individuals
Dwaipayan Adhya,Vivek Swarup,Roland Nagy,Lucia Dutan Polit,Carole Shum,Eva P. Valencia-Alarcón,Kamila M. Jozwik,Maria Andreina Mendez,Jamie Horder,Eva Loth,Paulina Nowosiad,Irene Lee,David Skuse,Frances Flinter,Declan G. Murphy,Grainne M. McAlonan,Daniel H. Geschwind,Jack Price,Jason S. Carroll,Deepak Srivastava,Simon Baron-Cohen +20 more
TL;DR: Data suggest unique developmental differences associated with autism may establish at an early prenatal stage, as differentiation of iPSCs towards a midbrain lineage was not accompanied by differences in neurogenesis between typically developing and autism iPSC lines.
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Optogenetics for neurodegenerative diseases.
Kiara T. Vann,Zhi-Gang Xiong +1 more
TL;DR: This review focuses on the recent advance in using Optogenetics, a recently developed novel technique that combines optics and genetics to modulate the activity of specific neurons, for the studies of common neurodegenerative diseases.
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Induced Pluripotent Stem Cells: A Powerful Neurodegenerative Disease Modeling Tool for Mechanism Study and Drug Discovery
Chia Yu Chang,Hsiao Chien Ting,Ching Ann Liu,Hong-Lin Su,Tzyy-Wen Chiou,Horng-Jyh Harn,Shinn Zong Lin +6 more
TL;DR: This review highlights neuronal differentiation methods and the current development of iPSC-based neurodegenerative disease modeling tools for mechanism study and drug screening, with a discussion of the challenges and future inspiration for application.
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Recovery from experimental parkinsonism by intrastriatal application of erythropoietin or EPO-releasing neural precursors.
Stephana Carelli,T. Giallongo,Cristina Viaggi,Elisa Latorre,Zuzana Gombalova,Andrea Raspa,Massimiliano Mazza,Francesca Vaglini,Anna Maria Di Giulio,Alfredo Gorio +9 more
TL;DR: It is shown that EPO, whether ectopically administered or released by neural precursors, does reverse MPTP‐induced parkinsonism in mice, and Er‐NPCs transplantation improves behavioral performances in parkinsonian mice.
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