Induced pluripotent stem cells as tools for disease modelling and drug discovery in Alzheimer’s disease

Ooi, Lezanne; Sidhu, Kuldip; Poljak, Anne; Sutherland, Greg T.; O’Connor, Michael D.; Sachdev, Perminder S.; Münch, Gerald

doi:10.1007/s00702-012-0839-2

Cited by 48 publications

(44 citation statements)

References 86 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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“…iPSCs, derived from the dermal fibroblasts of AD patients that differentiated into cholinergic neurons, might be a promising novel tool for disease modeling and drug discovery for the sporadic [61] and familial forms of AD [62] .…”

Section: (5) Induced Pluripotent Stem Cells (Ipscs)mentioning

confidence: 99%

Cell-based therapy in Alzheimer's disease: Current knowledge and perspective

Qiao

Huang²,

Chen

2016

Transl. Neurosci. Clin.

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KEYWORDSAlzheimer's disease; cell therapy; stem cells; neurogenesis Alzheimer's disease (AD) is the most prevalent type of dementia, and its neuropathology is characterized by the deposition of insoluble β-amyloid (Aβ) peptides, intracellular neurofibrillary tangles, amyloid angiopathy, age-related brain atrophy, synaptic pathology, white matter rarefaction, granulovacuolar degeneration, neuron loss, and neuroinflammation. Although much is known about the neurobiology of AD, very few conventional therapies are available to arrest or slow the disease. There is an urgent need for novel therapeutic approaches for AD. AD subjects have significantly fewer viable precursor cells in the hippocampus compared with age-matched healthy control subjects. However, the viable precursor cells that remain in AD and age-matched healthy control brain specimens can be induced to differentiate. To facilitate or mimic the natural compensatory effect in AD, cell therapy, including endogenous and exogenous stem cells, has been considered in AD. In this review, we focus on the history and development of cell therapy in AD, and consider the role of cell therapy as a potential treatment for AD.Citation Qiao LY, Huang HY, Chen L. Cell-based therapy in Alzheimer's disease: Current knowledge and perspective. Transl. Neurosci. Clin. 2016, 2(1): 50-58.

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“…hiPSCs have been generated from patients affected with either familial or late-onset AD and have been differentiated into electrophysiologically active neurons, recapitulating common features of AD, such as high level of A␤ , active glycogen synthase kinase 3␤, and p-tau [99], A␤ accumulation in neuronal cells and astrocytes, and endoplasmic reticulum oxidative stress [100]. Additionally, these differentiated neurons might be useful to identify the specific roles of cellular subtypes in the pathogenesis of AD, to obtain insights into patientspecific drug responses, for prospective diagnostics [101], and to assess the susceptibility of specific ADrelated genes [102]. More recently, reprogramming of AD patient-derived non-neuronal somatic cells into neuronal mature cells (iNCs) [98,103], AD patientderived olfactory mucosa stem cells [96], genetically modified human neural stem cells (NSCs) [19], and three-dimensional culture systems [104] have been applied.…”

Section: The Organ/tissue and Cellular Levels: Novel Human Stem Cell mentioning

confidence: 99%

A Human-Based Integrated Framework forAlzheimer’s Disease Research

Pistollato

Cavanaugh

Chandrasekera

2015

JAD

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Abstract. Animal models of Alzheimer's disease (AD) have been extensively utilized for decades in an effort to elucidate the pathophysiological mechanisms of this disease and to test novel therapeutic approaches. However, research success has not effectively translated into therapeutic success for human patients. This translational failure is partially due to the overuse of animal models that cannot accurately recapitulate human AD etiopathogenesis or drug responses and the inadequate use of human-relevant research methods. Here, we propose how to mitigate this translational barrier by employing human-based methods to elucidate disease processes occurring at multiple levels of complexity, accounting for gene and protein expression and the impact of disease at the cellular, tissue/organ, individual, and population levels. In particular, novel human-based cellular and computational models, together with epidemiological and clinical studies, represent the ideal tools to facilitate human-relevant data acquisition, in the effort to better elucidate AD pathogenesis in a human-based setting and design more effective treatments and preventive strategies. Our analysis indicates that a paradigm shift toward human-based, rather than animal-based research is required in the face of the ever-increasing prevalence of AD in the 21st century.

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Induced pluripotent stem cells as tools for disease modelling and drug discovery in Alzheimer’s disease

Cited by 48 publications

References 86 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

Cell-based therapy in Alzheimer's disease: Current knowledge and perspective

A Human-Based Integrated Framework forAlzheimer’s Disease Research

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