Using multi-organ culture systems to study Parkinson’s disease

Abstract

In recent years, it has been revealed that Parkinson's disease pathology may begin to manifest in the gastrointestinal track at a much earlier time point than in the brain. This paradigm shift has been suggested following evidence in humans that has been reproduced in animal models. Since rodent models cannot recapitulate many of the human disease features, human induced pluripotent stem cells derived from Parkinson's patients have been used to generate brain organoids, greatly contributing to our understanding of the disease pathophysiology. To understand the multifaced aspects of Parkinson's disease, it may be desirable to expand the complexity of these models, to include different brain regions, vasculature, immune cells as well as additional diverse organ-specific organoids such as gut and intestine. Furthermore, the contribution of gut microbiota to disease progression cannot be underestimated. Recent biotechnological advances propose that such combinations may be feasible. Here we discuss how this need can be met and propose that additional brain diseases can benefit from this approach.

The Microbiota–Gut–Brain Axis and Alzheimer Disease. From Dysbiosis to Neurodegeneration: Focus on the Central Nervous System Glial Cells

“…Human-induced pluripotent stem cell (iPSC) technology, a recent bioengineering technique, is considered a promising methodology to reproduce, in vitro, complex systems such as the microbiota–gut–brain and to connect them to each other. Further, iPSC can be utilized to differentiate all major brain cell types to study many neurodegenerative diseases [ 185 , 186 , 187 ]. Using iPSC-derived cells from normal and diseased patients, it is now possible to understand the complex cellular/molecular interplay that occurs between the different brain cell types in AD.…”

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

“…Recently, a study in 2017 modelled the growth and structural formation of the human cortex in vitro using cerebral three-dimensional organoids [117]. Gyrification and expansion were achieved Parkinson's disease multisystem organoid dopaminergic neurons organoids with distinct expression profiles of genes associated with synaptic transmission [111] neuroectodermal spheres LRRK2 (G2019S) neurons organoids with DARPP32 + neuros [112] HD striatal organoids Map2, ARPP32 organoids with neurons with CAG repeats over 100 [82,113] neurons with CAG repeats (Q109 and Q180)…”

Intestinal Stem Cell-on-Chip to Study Human Host-Microbiota Interaction

“…These gut-on-chip systems strikingly demonstrate the vast potential of organ-on-chip platforms to precisely control environmental growth conditions, to guide the differentiation of stem cells, and to form improved intrinsically self-organized tissue with superior properties compared to traditional organoid cultures. Hence, the applications of ISCs include the possibility to investigate intestinal developmental biology and barrier function but also studies related to bacterial colonization, drug discovery, regenerative medicine, and responses to infections in a personalized approach (40)(41)(42)(43). The generation and integration of hiPSC-derived immune cells such as T cells, NK cells, and macrophages by use of differentiation protocols that became recently available will aid in the development of isogenic immune-competent intestinal models derived from a single hiPSC line to avoid potential allogenic reactions (44)(45)(46).…”