Solving the puzzle of Parkinson’s disease using induced pluripotent stem cells

Zhao, Ping; Luo, Zhiwei; Tian, Weihua; Yang, Jiayin; Ibañez, David P.; Huang, Zhijian; Tortorella, Micky D.; Esteban, Miguel A.; Fan, Wenxia

doi:10.1177/1535370214538588

Cited by 16 publications

(10 citation statements)

References 79 publications

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“…In recent years, the potential of hiPS-derived neuronal cell models for drug safety testing and pathology development were discovered and implemented for Parkinson's (Zhao et al 2014) and Alzheimer's disease (Ooi et al 2013), amyotrophic lateral sclerosis (Richard and Maragakis 2014) and neurotoxicity screening (Scott et al 2013). …”

Section: Discussionmentioning

confidence: 99%

Impedimetric real-time monitoring of neural pluripotent stem cell differentiation process on microelectrode arrays

Seidel

Obendorf

Englich

et al. 2016

Biosensors and Bioelectronics

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In today's neurodevelopment and -disease research, human neural stem/progenitor cell-derived networks represent the sole accessible in vitro model possessing a primary phenotype. However, cultivation and moreover, differentiation as well as maturation of human neural stem/progenitor cells are very complex and time-consuming processes. Therefore, techniques for the sensitive non-invasive, real-time monitoring of neuronal differentiation and maturation are highly demanded. Using impedance spectroscopy, the differentiation of several human neural stem/progenitor cell lines was analyzed in detail. After development of an optimum microelectrode array for reliable and sensitive long-term monitoring, distinct cell-dependent impedimetric parameters that could specifically be associated with the progress and quality of neuronal differentiation were identified. Cellular impedance changes correlated well with the temporal regulation of biomolecular progenitor versus mature neural marker expression as well as cellular structure changes accompanying neuronal differentiation. More strikingly, the capability of the impedimetric differentiation monitoring system for the use as a screening tool was demonstrated by applying compounds that are known to promote neuronal differentiation such as the γ-secretase inhibitor DAPT. The non-invasive impedance spectroscopy-based measurement system can be used for sensitive and quantitative monitoring of neuronal differentiation processes. Therefore, this technique could be a very useful tool for quality control of neuronal differentiation and moreover, for neurogenic compound identification and industrial high-content screening demands in the field of safety assessment as well as drug development.

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Section: Discussionmentioning

confidence: 99%

Impedimetric real-time monitoring of neural pluripotent stem cell differentiation process on microelectrode arrays

Seidel

Obendorf

Englich

et al. 2016

Biosensors and Bioelectronics

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“…This platform recapitulates key features of PD, including degeneration of dopaminergic neurons and preceding mitochondrial impairments. [26] The successful use of 3D-derived and hNESC-derived neurons for phenotype assessment has been demonstrated with Alzheimer's disease. When considering all experiments at all time points, genetic background of the patients was found to be a major discriminating factor among the lines and not the LRRK2-G2019S mutation.…”

Section: Discussionmentioning

confidence: 99%

3D Cultures of Parkinson's Disease‐Specific Dopaminergic Neurons for High Content Phenotyping and Drug Testing

et al. 2018

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Parkinson's disease (PD)‐specific neurons, grown in standard 2D cultures, typically only display weak endophenotypes. The cultivation of PD patient‐specific neurons, derived from induced pluripotent stem cells carrying the LRRK2‐G2019S mutation, is optimized in 3D microfluidics. The automated image analysis algorithms are implemented to enable pharmacophenomics in disease‐relevant conditions. In contrast to 2D cultures, this 3D approach reveals robust endophenotypes. High‐content imaging data show decreased dopaminergic differentiation and branching complexity, altered mitochondrial morphology, and increased cell death in LRRK2‐G2019S neurons compared to isogenic lines without using stressor agents. Treatment with the LRRK2 inhibitor 2 (Inh2) rescues LRRK2‐G2019S‐dependent dopaminergic phenotypes. Strikingly, a holistic analysis of all studied features shows that the genetic background of the PD patients, and not the LRRK2‐G2019S mutation, constitutes the strongest contribution to the phenotypes. These data support the use of advanced in vitro models for future patient stratification and personalized drug development.

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“…The incidence of these diseases is expected to rise dramatically as life expectancy increases, which represents a significant economic and social burden. Animal models (e.g., transgenic animals or knockout animals) of neurodegenerative diseases have been generated to understand disease mechanisms and to provide a platform for testing therapeutic strategies [ 8 , 14 , 17 , 75 , 76 ] but the construction of models that can accurately and thoroughly reproduce human pathology remains problematic. Furthermore, due to species variation and differences in cell line specificity, there is substantial debate as to whether animal and cell line disease models accurately reflect the natural phenomena that occur in human patients [ 8 ].…”

Section: Applications Of Ipscs In Neurodegenerative Diseasesmentioning

confidence: 99%

Applications of Induced Pluripotent Stem Cells in Studying the Neurodegenerative Diseases

Wan

Cao

Kalionis

et al. 2015

Stem Cells International

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Neurodegeneration is the umbrella term for the progressive loss of structure or function of neurons. Incurable neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD) show dramatic rising trends particularly in the advanced age groups. However, the underlying mechanisms are not yet fully elucidated, and to date there are no biomarkers for early detection or effective treatments for the underlying causes of these diseases. Furthermore, due to species variation and differences between animal models (e.g., mouse transgenic and knockout models) of neurodegenerative diseases, substantial debate focuses on whether animal and cell culture disease models can correctly model the condition in human patients. In 2006, Yamanaka of Kyoto University first demonstrated a novel approach for the preparation of induced pluripotent stem cells (iPSCs), which displayed similar pluripotency potential to embryonic stem cells (ESCs). Currently, iPSCs studies are permeating many sectors of disease research. Patient sample-derived iPSCs can be used to construct patient-specific disease models to elucidate the pathogenic mechanisms of disease development and to test new therapeutic strategies. Accordingly, the present review will focus on recent progress in iPSC research in the modeling of neurodegenerative disorders and in the development of novel therapeutic options.

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Solving the puzzle of Parkinson’s disease using induced pluripotent stem cells

Cited by 16 publications

References 79 publications

Impedimetric real-time monitoring of neural pluripotent stem cell differentiation process on microelectrode arrays

Impedimetric real-time monitoring of neural pluripotent stem cell differentiation process on microelectrode arrays

3D Cultures of Parkinson's Disease‐Specific Dopaminergic Neurons for High Content Phenotyping and Drug Testing

Applications of Induced Pluripotent Stem Cells in Studying the Neurodegenerative Diseases

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