Age-related neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), continue to be formidable challenges to the global medical community. As the global population ages, the prevalence of these diseases is also expected to increase. One of the most significant challenges in the fight against these diseases is the lack of effective cell-based models that can accurately recapitulate the complex pathophysiology observed in human patients. However, with recent advancements in stem cell technology, particularly human pluripotent stem cells (hPSCs), there is a beacon of hope.
This Research Topic, titled “Cell-Based Neurodegenerative Disease Modeling,” brings together an array of studies that showcases the current strides in developing, improving, and validating cell-based neurodegenerative disease models. This is a collation of pioneering research articles and reviews from experts in the field, providing insights, methodologies, and challenges pertinent to the cellular models of these debilitating diseases.
In a comprehensive review, Lin et al. have investigated the potential of cellular therapy for ALS, a disease with unclear pathology and ineffective therapeutic modalities. They emphasized the immunomodulatory effects and potential protective measures of cellular therapy for motor neuron circuits in ALS while highlighting the ongoing debates on the safety and efficacy of such interventions.
Further advancing our understanding of PD, a Lewy body disease, Natalwala et al. have reported the development of an isogenic Research Topic method of pluripotent stem cell lines with elevated α-synuclein expression. Their findings reinforce the capability of pluripotent stem cell lines, even with increased α-synuclein levels, to efficiently differentiate into dopaminergic and cortical neurons. Such models have become invaluable tools for studying PD-associated early molecular changes.
Sibuea et al. have studied the complex territory of maturation in stem cell-derived dopaminergic neuron. They have meticulously investigated the role of culture additives commonly used in maturation, like dbcAMP and TGFβ3, shedding light on their nuanced impact on the phenotype of midbrain dopaminergic neurons, thereby offering a fresh perspective on the current protocols.
Drawing attention to the critical role of endoplasmic reticulum–mitochondrial contact sites (ERMCS) in neurodegenerative diseases, Yokota et al. have employed tyrosine hydroxylase reporter iPSC lines to elucidate the aberrations in ERMCS and mitochondrial Ca2+ flux in PRKN-mutant patient dopaminergic neurons. These findings emphasize the significance of studying the ERMCS to enhance our understanding of dopaminergic neuronal degeneration in specific patient populations.
Moon et al. have holistically reviewed the intricate challenges associated with cell therapy for PD using hPSCs. By focusing on in vivo differentiation protocols and transplantation results, they underscored the potential of hPSC-derived ventral midbrain dopaminergic progenitors for PD treatment, while simultaneously focusing on current hurdles, such as lineage identification.
This Research Topic of articles emphasizes the critical importance and urgency of refining and developing cell-based models, particularly those based on hPSCs, to emulate human neurodegenerative diseases. These models, as shown in this Research Topic, not only provide invaluable insights into disease pathogenesis, but also present an avenue for testing potential therapeutic interventions.
In conclusion, as the gap between traditional animal and human cell models continues to widen, pioneering studies such as those presented here have become vital. I hope that this compilation will serve as a touchstone for future endeavors in neurodegenerative disease modeling and therapeutics.
Statements
Acknowledgments
The author expresses their deepest gratitude to all contributors for their insightful research on this Research Topic. Special thanks are also extended to the reviewers and other Research Topic editors who provided critical insights and feedback, which has greatly enhanced the quality of this Research Topic. My heartfelt appreciation goes to the editorial staff at Frontiers in Cell and Developmental Biology for their assistance and support throughout the publication process.
Conflict of interest
The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Summary
Keywords
neurodegenerative disease, disease modeling, human pluripotent stem cell, cell therapy, Parkinson’s diseae, amyotrophic lateral sclerosis
Citation
Oh Y (2023) Editorial: Cell-based neurodegenerative disease modeling. Front. Cell Dev. Biol. 11:1323954. doi: 10.3389/fcell.2023.1323954
Received
18 October 2023
Accepted
20 October 2023
Published
26 October 2023
Volume
11 - 2023
Edited and reviewed by
Valerie Kouskoff, The University of Manchester, United Kingdom
Updates
Copyright
© 2023 Oh.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Yohan Oh, yoh@hanyang.ac.kr
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.