Induced Pluripotent Stem Cells and Their Applications in Amyotrophic Lateral Sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that results in the loss of motor function in the central nervous system (CNS) and ultimately death. The mechanisms underlying ALS pathogenesis have not yet been fully elucidated, and ALS cannot be treated effectively. Most studies have applied animal or single-gene intervention cell lines as ALS disease models, but they cannot accurately reflect the pathological characteristics of ALS. Induced pluripotent stem cells (iPSCs) can be reprogrammed from somatic cells, possessing the ability to self-renew and differentiate into a variety of cells. iPSCs can be obtained from ALS patients with different genotypes and phenotypes, and the genetic background of the donor cells remains unchanged during reprogramming. iPSCs can differentiate into neurons and glial cells related to ALS. Therefore, iPSCs provide an excellent method to evaluate the impact of diseases on ALS patients. Moreover, patient-derived iPSCs are obtained from their own somatic cells, avoiding ethical concerns and posing only a low risk of immune rejection. The iPSC technology creates new hope for ALS treatment. Here, we review recent studies on iPSCs and their applications in disease modeling, drug screening and cell therapy in ALS, with a particular focus on the potential for ALS treatment.

Rapid and Robust Multi-Phenotypic Assay System for ALS Using Human iPS Cells with Mutations in Causative Genes

“…For this reason, induced pluripotent stem cell (iPSC) models have become increasingly important in ALS research because they provide a valuable tool to study the cellular and molecular mechanisms underlying this complex disease. By using iPSCs, researchers can generate motor neurons that are affected by ALS and study them in the laboratory, which can provide insights into the disease’s underlying mechanisms and potential treatments [ 3 ].…”

Meta-analysis of differential gene expression in lower motor neurons isolated by laser capture microdissection from post-mortem ALS spinal cords

“…Third, iPSC-MNs may be better suited as a model for embryonic-stage motor neurons, with limited ability to replicate many of the disease-related expression shifts seen in postmitotic motor neurons targeted by LCM analysis of post-mortem tissues ( Ho et al, 2016 ). For these reasons, baseline differences between ALS and CTL iPSC-MNs may not parallel those of mature in situ motor neurons, although iPSC-MNs may still provide a flexible and valuable in vitro system for certain research objectives ( Du et al, 2023 ).…”

Standardisation is the key to the sustained, rapid and healthy development of stem cell‐based therapy

“…IPSCs can be obtained from amyotrophic lateral sclerosis (ALS) patients with different genetic phenotypes, and the genetic background of the cells is not affected by the reprogramming process. 96 Therefore, iPSCs can well assess the impact of ALS on patients and accelerate ALS in vitro modelling and drug development. 96 , 97 Notably, transplantation of iPSCs‐derived glial cells rather than derived motor neurons can treat ALS by improving the neuronal environment.…”

“… 96 Therefore, iPSCs can well assess the impact of ALS on patients and accelerate ALS in vitro modelling and drug development. 96 , 97 Notably, transplantation of iPSCs‐derived glial cells rather than derived motor neurons can treat ALS by improving the neuronal environment. 96 In clinical practice, ASCs are the most studied.…”

“… 96 , 97 Notably, transplantation of iPSCs‐derived glial cells rather than derived motor neurons can treat ALS by improving the neuronal environment. 96 In clinical practice, ASCs are the most studied. Researchers are harnessing the regenerative capabilities of ASCs to treat many diseases such as heart, brain, pancreatic and eye diseases.…”