An insight into the iPSCs-derived two-dimensional culture and three-dimensional organoid models for neurodegenerative disorders.

The use of induced pluripotent stem cells (iPSCs) is a promising approach when used as models to study neurodegenerative disorders (NDDs) in vitro. iPSCs have been used in in vitro two-dimensional cultures; however, these two-dimensional cultures do not mimic the physiological three-dimensional cellular environment. The use of iPSCs-derived three-dimensional organoids has risen as a powerful alternative to using animal models to study NDDs. These iPSCs-derived three-dimensional organoids can resemble the complexity of the tissue of interest, making it an approachable, cost-effective technique, to study NDDs in an ethical manner. Furthermore, the use of iPSCs-derived organoids will be an important tool to develop new therapeutics and pharmaceutics to treat NDDs. Herein, we will highlight how iPSCs-derived two-dimensional cultures and three-dimensional organoids have been used to study NDDs, as well as the advantages and disadvantages of both techniques.

Modeling tuberous sclerosis complex with human induced pluripotent stem cells.

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder with a birth incidence of 1:6000 in the United States that is characterized by the growth of non-cancerous tumors in multiple organ systems including the brain, kidneys, lungs, and skin. Importantly, TSC is also associated with significant neurological manifestations including epilepsy, TSC-associated neuropsychiatric disorders, intellectual disabilities, and autism spectrum disorder. Mutations in the TSC1 or TSC2 genes are well-established causes of TSC, which lead to TSC1/TSC2 deficiency in organs and hyper-activation of the mammalian target of rapamycin signaling pathway. Animal models have been widely used to study the effect of TSC1/2 genes on the development and function of the brain. Despite considerable progress in understanding the molecular mechanisms underlying TSC in animal models, a human-specific model is urgently needed to investigate the effects of TSC1/2 mutations that are unique to human neurodevelopment. DATA SOURCES: Literature reviews and research articles were published in PubMed-indexed journals. RESULTS: Human-induced pluripotent stem cells (iPSCs), which capture risk alleles that are identical to their donors and have the capacity to differentiate into virtually any cell type in the human body, pave the way for the empirical study of previously inaccessible biological systems such as the developing human brain. CONCLUSIONS: In this review, we present an overview of the recent progress in modeling TSC with human iPSC models, the existing limitations, and potential directions for future research.

Cell Culture Based in vitro Test Systems for Anticancer Drug Screening.

The development of new high-tech systems for screening anticancer drugs is one of the main problems of preclinical screening. Poor correlation between preclinical in vitro and in vivo data with clinical trials remains a major concern. The choice of the correct tumor model at the stage of in vitro testing provides reduction in both financial and time costs during later stages due to the timely screening of ineffective agents. In view of the growing incidence of oncology, increasing the pace of the creation, development and testing of new antitumor agents, the improvement and expansion of new high-tech systems for preclinical in vitro screening is becoming very important. The pharmaceutical industry presently relies on several widely used in vitro models, including two-dimensional models, three-dimensional models, microfluidic systems, Boyden's chamber and models created using 3D bioprinting. This review outlines and describes these tumor models including their use in research, in addition to their characteristics. This review therefore gives an insight into in vitro based testing which is of interest to researchers and clinicians from differing fields including pharmacy, preclinical studies and cell biology.

Relevance of bioreactors and whole tissue cultures for the translation of new therapies to humans.

The purpose of this review is to provide a brief overview of bioreactor-based culture systems as alternatives to conventional two- and three-dimensional counterparts. The role, challenges, and future aspirations of bioreactors in the musculoskeletal field (e.g., cartilage, intervertebral disc, tendon, and bone) are discussed. Bioreactors, by recapitulating physiological processes, can be used effectively as part of the initial in vitro screening, reducing that way the number of animal required for preclinical assessment, complying with the 3R principles and, in most cases, allowing working with human tissues. The clinical significance of bioreactors is that, by providing more physiologically relevant conditions to customarily used two- and three-dimensional cultures, they hold the potential to provide a testing platform that is more predictable of a whole tissue response, thereby facilitating the screening of treatments before the initiation of clinical trials. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:10-21, 2018.