International Journal of Molecular Sciences

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Special Issue Editor

Dr. Alessandro Romano

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Guest Editor

Division of Neuroscience, Experimental Neurology Unit, San Raffaele Scientific Institute, 20132 Milano, Italy
Interests: neurodegenerative disesases; amyotropic lateral sclerosis (ALS); human induced pluripotent stem cell models of disease; extracellular vesicles; protein aggregation; RNA metabolism
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neurodegenerative diseases are neurological disorders characterized by the progressive degeneration of neurons in central and peripheral nervous systems. These diseases are one of the leading causes of mental and physical disability among elderly people and today represent a major challenge for society and healthcare systems. Despite extensive research efforts, the lack of experimental models able to adequately replicate human neurodegenerative diseases represents a major obstacle to fully dissecting the cellular/molecular mechanisms involved in the pathogenesis of these diseases and developing effective therapies for their treatment.

Recently, several technologies such as induced pluripotent stem cell (iPSC), hydrogel-based three-dimensional cell culture, advanced imaging, microfluidics, and nanofabrication have been combined with the aim of providing new and reliable in vitro models for the study of neurodegenerative diseases. The ambitious goal of these research efforts is the development of organ-on-a-chip (OoC) platforms capable of reproducing, at least in part, the complex interactions that occur among the different cells/components of the central and peripheral nervous systems.

This Special Issue aims to collect and publish the latest research trends within OoC technologies focusing on molecular technologies developed specifically to model neurodegenerative diseases. We would like to invite authors to submit original research articles and reviews exploring the use of advanced technologies to model central and peripheral nervous systems and to study the pathogenic mechanisms and the therapeutic strategies of neurodegenerative diseases. OoC platforms that model the blood–brain barrier and the blood–nerve barrier in the context of neurodegenerative diseases are also within the scope of the Special Issue. Moreover, articles and reviews discussing the use of 3D bioprinting technologies and nanotechnology-based biosensors for the development of OoC models of neurodegenerative diseases are also welcome.

Dr. Alessandro Romano
Guest Editor

Manuscript Submission Information

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Keywords

neurodegenerative diseases
central nervous system
peripheral nervous system
blood–brain barrier
blood–nerve barrier
induced pluripotent stem cell (iPSC)
three-dimensional cell culture
nanofabrication
microfluidics
organ-on-a-chip (OoC)

Published Papers (2 papers)

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Research

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18 pages, 1926 KiB

Open AccessArticle

Human Neurons Form Axon-Mediated Functional Connections with Human Cardiomyocytes in Compartmentalized Microfluidic Chip

by Martta Häkli, Satu Jäntti, Tiina Joki, Lassi Sukki, Kaisa Tornberg, Katriina Aalto-Setälä, Pasi Kallio, Mari Pekkanen-Mattila and Susanna Narkilahti

Int. J. Mol. Sci. 2022, 23(6), 3148; https://doi.org/10.3390/ijms23063148 - 15 Mar 2022

Cited by 5 | Viewed by 4055

Abstract

The cardiac autonomic nervous system (cANS) regulates cardiac function by innervating cardiac tissue with axons, and cardiomyocytes (CMs) and neurons undergo comaturation during the heart innervation in embryogenesis. As cANS is essential for cardiac function, its dysfunctions might be fatal; therefore, cardiac innervation models for studying embryogenesis, cardiac diseases, and drug screening are needed. However, previously reported neuron-cardiomyocyte (CM) coculture chips lack studies of functional neuron–CM interactions with completely human-based cell models. Here, we present a novel completely human cell-based and electrophysiologically functional cardiac innervation on a chip in which a compartmentalized microfluidic device, a 3D3C chip, was used to coculture human induced pluripotent stem cell (hiPSC)-derived neurons and CMs. The 3D3C chip enabled the coculture of both cell types with their respective culture media in their own compartments while allowing the neuronal axons to traverse between the compartments via microtunnels connecting the compartments. Furthermore, the 3D3C chip allowed the use of diverse analysis methods, including immunocytochemistry, RT-qPCR and video microscopy. This system resembled the in vivo axon-mediated neuron–CM interaction. In this study, the evaluation of the CM beating response during chemical stimulation of neurons showed that hiPSC-neurons and hiPSC-CMs formed electrophysiologically functional axon-mediated interactions. Full article

(This article belongs to the Special Issue Advanced Models of Neurodegenerative Diseases: From Induced Pluripotent Stem Cells to Organ-on-a-Chips)

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Graphical abstract

Review

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18 pages, 2246 KiB

Open AccessReview

Stem Cells in Clinical Trials on Neurological Disorders: Trends in Stem Cells Origins, Indications, and Status of the Clinical Trials

by Eugenia D. Namiot, Jenni Viivi Linnea Niemi, Vladimir N. Chubarev, Vadim V. Tarasov and Helgi B. Schiöth

Int. J. Mol. Sci. 2022, 23(19), 11453; https://doi.org/10.3390/ijms231911453 - 28 Sep 2022

Cited by 4 | Viewed by 2732

Abstract

Neurological diseases can significantly reduce the quality and duration of life. Stem cells provide a promising solution, not only due to their regenerative features but also for a variety of other functions, including reducing inflammation and promoting angiogenesis. Although only hematopoietic cells have been approved by the FDA so far, the number of trials continues to expand. We analyzed 492 clinical trials and illustrate the trends in stem cells origins, indications, and phase and status of the clinical trials. The most common neurological disorders treated with stem cells were injuries of brain, spinal cord, and peripheral nerves (14%), stroke (13%), multiple sclerosis (12%), and brain tumors (11%). Mesenchymal stem cells dominated (83%) although the choice of stem cells was highly dependent on the neurological disorder. Of the 492 trials, only two trials have reached phase 4, with most of all other trials being in phases 1 or 2, or transitioning between them (83%). Based on a comparison of the obtained results with similar works and further analysis of the literature, we discuss some of the challenges and future directions of stem cell therapies in the treatment of neurological diseases. Full article

(This article belongs to the Special Issue Advanced Models of Neurodegenerative Diseases: From Induced Pluripotent Stem Cells to Organ-on-a-Chips)

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