2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there are no therapeutic cures available. Even though animal and histological models have been of great aid in understanding disease mechanisms and identifying possible therapeutic strategies, in order to find disease-modifying solutions there is still a critical need for systems that can provide more predictive and physiologically relevant results. One possible avenue is the development of patient-derived models, e.g. by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), which can then be differentiated into any cell type for modelling. These systems contain key genetic information from the donors, and therefore have enormous potential as tools in the investigation of pathological mechanisms underlying disease phenotype, and progression, as well as in drug testing platforms. hiPSCs have been widely cultured in 2D systems, but in order to mimic human brain complexity, 3D models have been proposed as a more advanced alternative. This review will focus on the use of patient-derived hiPSCs to model AD, PD, HD and ALS. In brief, we will cover the available stem cells, types of 2D and 3D culture systems, existing models for neurodegenerative diseases, obstacles to model these diseases in vitro, and current perspectives in the field

A graphene-based electrochemical device with thermoresponsive microneedles for diabetes monitoring and therapy

Owing to its high carrier mobility, conductivity, flexibility and optical transparency, graphene is a versatile material in micro- and macroelectronics. However, the low density of electrochemically active defects in graphene synthesized by chemical vapour deposition limits its application in biosensing. Here, we show that graphene doped with gold and combined with a gold mesh has improved electrochemical activity over bare graphene, sufficient to form a wearable patch for sweat-based diabetes monitoring and feedback therapy. The stretchable device features a serpentine bilayer of gold mesh and gold-doped graphene that forms an efficient electrochemical interface for the stable transfer of electrical signals. The patch consists of a heater, temperature, humidity, glucose and pH sensors and polymeric microneedles that can be thermally activated to deliver drugs transcutaneously. We show that the patch can be thermally actuated to deliver Metformin and reduce blood glucose levels in diabetic mice.N

Neural In Vitro Models for Studying Substances Acting on the Central Nervous System

Animal models have been greatly contributing to our understanding of physiology, mechanisms of diseases, and toxicity. Yet, their limitations due to, e.g., interspecies variation are reflected in the high number of drug attrition rates, especially in central nervous system (CNS) diseases. Therefore, human-based neural in vitro models for studying safety and efficacy of substances acting on the CNS are needed. Human iPSC-derived cells offer such a platform with the unique advantage of reproducing the "human context" in vitro by preserving the genetic and molecular phenotype of their donors. Guiding the differentiation of hiPSC into cells of the nervous system and combining them in a 2D or 3D format allows to obtain complex models suitable for investigating neurotoxicity or brain-related diseases with patient-derived cells. This chapter will give an overview over stem cell-based human 2D neuronal and mixed neuronal/astrocyte models, in vitro cultures of microglia, as well as CNS disease models and considers new developments in the field, more specifically the use of brain organoids and 3D bioprinted in vitro models for safety and efficacy evaluation