iPS-derived neural stem cells for disease modeling and evaluation of therapeutics for mucopolysaccharidosis type II

Hong, Junjie; Cheng, Yu‐Shan; Yang, Shu; Swaroop, Manju; Xu, Miao; Beers, Jeanette; Zou, Jizhong; Huang, Wenwei; Marugán, Juan; Cai, Xiujun; Zheng, Wei

doi:10.1016/j.yexcr.2021.113007

Cited by 9 publications

(12 citation statements)

References 51 publications

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“…Those observations further support the assumption that abnormal Lamp1 staining in MPS II correlates with lysosomal dysfunction [ 56 ]. Altered staining patterns for both LAMP1 and LAMP2 were also observed in MPS II iPSC-derived neural stem cells [ 21 ]. Remarkably, however, this pattern was not seen in all MPS II-derived neural stem cells reported so far.…”

Section: Discussionmentioning

confidence: 99%

“…However, disruptions of the glycosphingolipid degradation pathways are implicated not only in glycophingolipidoses but also in other LSDs, including MPSs [ 15 ]. And it is true that not only there is a well-documented secondary accumulation of lipids in MPS diseases (MPS II included) [ 21 , 58 ] but also there is an increasing body of evidence documenting significant elevations of several glycophingolipidose biomarkers in other LSDs, including neuronopathic forms of MPSs [ 59 ]. That is why we tried to address the question of whether any of those biomarkers could be altered in the cell lines under analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Altogether, the need for deeper understanding of the pathophysiological mechanisms that underlie the disorder and for more effective treatments to counteract it justify the need for a cellular in vitro model that accurately recapitulates the disease phenotype in hard-to-reach/hard-to-treat cells, e.g., those derived from the nervous and/or skeletal systems. Regarding neurons in particular, the use of induced pluripotent stem cells (iPSCs) to model neurogenetic disorders is well established, for example, the function of cortical neurons from patient-derived fibroblasts or blood cells is now well documented and numerous studies in MPS II-derived iPSCs have already been published, with remarkable results and insights on the neuropathology of this disorder [ 19 , 20 , 21 ] (reviewed in [ 22 ]). However, there are notable drawbacks to using these de-differentiated, reprogrammed cells as in vitro models for molecular studies, mostly their high cost and time-consuming technology validation.…”

Section: Introductionmentioning

confidence: 99%

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Modeling Lysosomal Storage Disorders in an Innovative Way: Establishment and Characterization of Stem Cell Lines from Human Exfoliated Deciduous Teeth of Mucopolysaccharidosis Type II Patients

Carvalho,

Santos,

Moreira

et al. 2024

IJMS

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Among the many lysosomal storage disorders (LSDs) that would benefit from the establishment of novel cell models, either patient-derived or genetically engineered, is mucopolysaccharidosis type II (MPS II). Here, we present our results on the establishment and characterization of two MPS II patient-derived stem cell line(s) from deciduous baby teeth. To the best of our knowledge, this is the first time a stem cell population has been isolated from LSD patient samples obtained from the dental pulp. Taking into account our results on the molecular and biochemical characterization of those cells and the fact that they exhibit visible and measurable disease phenotypes, we consider these cells may qualify as a valuable disease model, which may be useful for both pathophysiological assessments and in vitro screenings. Ultimately, we believe that patient-derived dental pulp stem cells (DPSCs), particularly those isolated from human exfoliated deciduous teeth (SHEDs), may represent a feasible alternative to induced pluripotent stem cells (iPSCs) in many labs with standard cell culture conditions and limited (human and economic) resources.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Modeling Lysosomal Storage Disorders in an Innovative Way: Establishment and Characterization of Stem Cell Lines from Human Exfoliated Deciduous Teeth of Mucopolysaccharidosis Type II Patients

Carvalho,

Santos,

Moreira

et al. 2024

IJMS

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show abstract

“…In fact, those two compounds have already shown positive results in Niemann–Pick disease type C and, more recently, also in other LSDs [ 69 , 70 , 71 ]. Due to this observation, both compounds were also evaluated in MPS II iPSC-derived NSCs by Hong et al [ 72 ]. In the case of DT, the results showed a reduction in lipid accumulation after three days, but in a dose-dependent manner; in turn, when evaluating the lysosomal accumulation, only a 7% reduction was revealed.…”

Section: Modeling Mucopolysaccharidoses With Induced Pluripotent Stem...mentioning

confidence: 99%

Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step towards Understanding and Treating Mucopolysaccharidoses

et al. 2023

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Despite extensive research, the links between the accumulation of glycosaminoglycans (GAGs) and the clinical features seen in patients suffering from various forms of mucopolysaccharidoses (MPSs) have yet to be further elucidated. This is particularly true for the neuropathology of these disorders; the neurological symptoms are currently incurable, even in the cases where a disease-specific therapeutic approach does exist. One of the best ways to get insights on the molecular mechanisms driving that pathogenesis is the analysis of patient-derived cells. Yet, not every patient-derived cell recapitulates relevant disease features. For the neuronopathic forms of MPSs, for example, this is particularly evident because of the obvious inability to access live neurons. This scenario changed significantly with the advent of induced pluripotent stem cell (iPSC) technologies. From then on, a series of differentiation protocols to generate neurons from iPSC was developed and extensively used for disease modeling. Currently, human iPSC and iPSC-derived cell models have been generated for several MPSs and numerous lessons were learnt from their analysis. Here we review most of those studies, not only listing the currently available MPS iPSC lines and their derived models, but also summarizing how they were generated and the major information different groups have gathered from their analyses. Finally, and taking into account that iPSC generation is a laborious/expensive protocol that holds significant limitations, we also hypothesize on a tempting alternative to establish MPS patient-derived neuronal cells in a much more expedite way, by taking advantage of the existence of a population of multipotent stem cells in human dental pulp to establish mixed neuronal and glial cultures.

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“…In fact, those two compounds have already positive results in Niemann-Pick disease type C and, more recently, also in other LSDs [130][131][132]. Due to this observation, both compounds were also evaluated in MPS II iPSCs-derived NSCs by Hong et al [133]. In the case of DT, the results showed a reduction of lipid accumulation after three days, but in a dose-dependent manner; in turn, when evaluating the lysosomal accumulation it was revealed only a 7% reduction.…”

Section: Ipscs-derived Neuronal Cells For Drug Screening/ Therapies E...mentioning

confidence: 99%

Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step Towards Understanding and Treating Mucopolysaccharidoses

Carvalho¹,

Santos²,

Moreira³

et al. 2023

Preprint

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Despite extensive research, the links between the accumulation of glycosaminoglycans (GAGs) and the clinical features seen in patients suffering from various forms of Mucopolysaccharidoses (MPSs) have yet to be further elucidated. This is particularly true for the neuropathology of these disorders, even though the neurological symptoms are currently incurable, even in the cases where a dis-ease-specific therapeutic approach does exist. One of the best ways to get insights on the molecular mechanisms driving that pathogenesis is the analysis of patient-derived cells. Yet, not every pa-tient-derived cell holds potential to recapitulate relevant disease features. For the neurodegenerative forms of these diseases in particular, it is challenging to grow neuronal cultures that accurately represent them because of the obvious inability to access live neurons. This scenario changed sig-nificantly since Yamanaka et al. published their protocol for induction of pluripotent stem cells (SC) from adult human fibroblasts. From then on, a series of differentiation protocols to generate neurons from induced pluripotent stem cells (iPSC) was developed and extensively used for disease mod-eling. Currently, human iPSC and iPSC-derived cell models have been generated for several MPS and numerous lessons were learnt from their analysis. Here we review most of those studies, not only listing the currently available MPS iPSC lines and their derived models, but also summarizing how they were generated and the major information different groups have gathered from their analysis. Finally, and taking into account that iPSC generation is a laborious/expensive protocol that holds significant limitations, we also comment on a tempting alternative to establish MPS pa-tient-derived neuronal cells in a much more expedite way by taking advantage of the existence of a population of multipotent SC in human dental pulp, to establish mixed neuronal and glial cultures.

show abstract

iPS-derived neural stem cells for disease modeling and evaluation of therapeutics for mucopolysaccharidosis type II

Cited by 9 publications

References 51 publications

Modeling Lysosomal Storage Disorders in an Innovative Way: Establishment and Characterization of Stem Cell Lines from Human Exfoliated Deciduous Teeth of Mucopolysaccharidosis Type II Patients

Modeling Lysosomal Storage Disorders in an Innovative Way: Establishment and Characterization of Stem Cell Lines from Human Exfoliated Deciduous Teeth of Mucopolysaccharidosis Type II Patients

Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step towards Understanding and Treating Mucopolysaccharidoses

Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step Towards Understanding and Treating Mucopolysaccharidoses

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