However, one disadvantage of vhCOs is that they lack blood cells within their vascular structures. chronic inflammatory neurodegenerative disease affecting young adults. models, three-dimensional culture, induced pluripotent stem cells, organoids Introduction Neurodegenerative diseases are age-related conditions characterized by uncontrolled neuronal death leading to a progressive decline in brain functions. These incurable and debilitating diseases are associated with a wide spectrum of clinical symptoms, including cognitive decline and/or the loss of locomotor functions. The number of affected individuals is growing due to the aging of human populations, and Ro 32-3555 the severe effects of such diseases on the quality of life have increased the burden on healthcare systems worldwide (Heemels, 2016). Dementias in particular are responsible for the greatest burden of age-related neurodegenerative diseases. This is a broad term used to describe a number of conditions characterized Ro 32-3555 by cognitive deficits, including Alzheimers disease (AD), vascular dementia, frontotemporal dementia, mixed dementia, and dementia with Lewy bodies. Other neurodegenerative diseases principally affect the locomotor system, including amyotrophic lateral sclerosis, Huntingtons Ro 32-3555 disease, Parkinsons disease (PD), multiple sclerosis (MS), and spinocerebellar ataxias. The limited efficacy of drugs for the treatment of neurodegenerative diseases reflects their complex etiology and pathogenesis. In addition to aging, multiple risk factors contribute to susceptibility including environmental triggers and genetic factors. Therefore, more work is Rabbit polyclonal to Osteopontin required to identify the underlying molecular mechanisms and corresponding pharmacological targets. In addition to the ethical concerns of animal experiments for medical research, the recent failure of several clinical trials targeting neurodegenerative diseases has raised doubts about the translatability of animal disease models to human patients, creating a demand for better research tools in this field (Olanow et al., 2008; Cummings et al., 2014; Schneider et al., 2014; Pfeuffer et al., 2016; Anderson et al., 2017). The development of novel models with greater physiological relevance may bridge the gap between current pre-clinical animal models and humans, allowing the discovery of promising drug targets that can be tested in future clinical trials. In addition, testing can reduce the duration and costs of translation by helping to identify the mechanism of action together with any associated risks. Several approaches have been developed to understand the etiology and pathogenesis of a broad range of neurodegenerative diseases (Table 1) and we focus on those applied to PD, AD, prion diseases and MS in this review. In 1962 the first CNS organotypic culture was prepared from Ro 32-3555 rat hypophysis tissue (Bousquet and Meunier, 1962). Cells derived from embryonic rat spinal cord and ganglia were subsequently cultured on collagen-coated glass, revealing their potential for organotypic differentiation and bioelectric properties suitable for electrophysiological studies (Crain, 1966). Since then, organotypic cultures have been prepared from brain slices encompassing several cerebral areas, including the hippocampus, substantia nigra, locus coeruleus, striatum, and basal forebrain (Lavail and Wolf, 1973; Whetsell and Schwarcz, 1983; Knopfel et al., 1989; Ostergaard et al., 1995; Robertson et al., 1997). Although tissue explants and organotypic slice cultures faithfully represent the cerebral architecture, they are difficult to prepare and maintain in a viable state, and their inherent variability leads to a lack of reproducibility in experiments (Walsh et al., 2005). The development of immortalized cell lines (Table 1) removed the need to use tissue as a source, but such cell lines often present genetic and metabolic abnormalities compared to normal human cells (Gordon et al., 2014). The advent of human embryonic stem cells (ESCs) and then human induced pluripotent stem cells (iPSCs) (Thomson et al., 1998; Takahashi et al., 2007) provided researchers with the tools to generate multiple differentiated cell types with the same genotype. Methods for the conversion of human somatic cells into iPSCs using retroviral transduction and transcription factors such as OCT4, SOX2, KLF4,.