Generation of human induced pluripotent stem cells (hIPSCs) from sialidosis types I and II patients with pathogenic neuraminidase 1 mutations

Han, Min‐Joon; Annunziata, Ida; Weesner, Jason Andrew; Campos, Yvan; Salie, Muneeb; O’Reilly, Carla; d’Azzo, Alessandra

doi:10.1016/j.scr.2020.101836

Cited by 4 publications

(4 citation statements)

References 5 publications

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“…A Trilineage Differentiation Kit (Ward et al, 2017) (STEMCELL, #05230) was used to induce differentiation into the three germ layers. Human three Germ Layer 3-Color Immunocytochemistry Kit (Han et al, 2020) (R&D, SC022) was used to identify specific protein markers of the three germ layers. A Giemsa Stain solution (Solarbio, G1015) was used to analyze the karyotype.…”

Section: Hipsc Identificationmentioning

confidence: 99%

Safety and biodistribution of exosomes derived from human induced pluripotent stem cells

Yin

Song

et al. 2022

Front. Bioeng. Biotechnol.

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As a new cell-free therapy, exosomes have provided new ideas for the treatment of various diseases. Human induced pluripotent stem cells (hiPSCs) cannot be used in clinical trials because of tumorigenicity, but the exosomes derived from hiPSCs may combine the advantages of iPSC pluripotency and the nanoscale size of exosomes while avoiding tumorigenicity. Currently, the safety and biodistribution of hiPSC-exosomes in vivo are unclear. Here, we investigated the effects of hiPSC-exosomes on hemolysis, DNA damage, and cytotoxicity through cell experiments. We also explored the safety of vein injection of hiPSC-exosomes in rabbits and rats. Differences in organ distribution after nasal administration were compared in normal and Parkinson’s disease model mice. This study may provide support for clinical therapy and research of intravenous and nasal administration of hiPSC-exosomes.

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Section: Hipsc Identificationmentioning

confidence: 99%

Safety and biodistribution of exosomes derived from human induced pluripotent stem cells

Yin

Song

et al. 2022

Front. Bioeng. Biotechnol.

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“…Sialidosis-iPSCs, harboring both sialidosis-associated mutations and patient-specific genetic background, offer emerging opportunities to investigate sialidosis at the cellular and molecular level. However, only four reports have been published on sialidosis-iPSC models from patients with different NEU1 mutations [ 21 , 22 , 23 , 24 ]. Two reports demonstrated the establishment of sialidosis-iPSC models with NEU1 mutations c.649G > A/644 T > C, c.1109A > G/c.1109A > G [ 43 ], c.1195_1200dup/c.679G > A [ 23 , 32 ], or c.544 A > G transition and 667–679 deletion from sialidosis patient fibroblasts [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…Development of neural lineage cells from disease-specific iPSCs, particularly those derived from neuropathic LSD patients, has contributed to a greater understanding of the neuropathophysiology of LSDs, yielding an effective cellular platform for identifying safer and more effective therapeutic targets [ 16 , 17 , 18 , 19 , 20 ]. Likewise, the development of sialidosis- and tissue-specific cells from iPSCs with sialidosis-associated mutations also offer emerging opportunities to investigate sialidosis at the cellular and molecular level, but they are less studied than other LSDs [ 21 , 22 , 23 , 24 ]. However, there have been a limited number of modeling studies for sialidosis.…”

Section: Introductionmentioning

confidence: 99%

Modeling Sialidosis with Neural Precursor Cells Derived from Patient-Derived Induced Pluripotent Stem Cells

Seol

Kim

Cho

2021

IJMS

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Sialidosis, caused by a genetic deficiency of the lysosomal sialidase gene (NEU1), is a systemic disease involving various tissues and organs, including the nervous system. Understanding the neurological dysfunction and pathology associated with sialidosis remains a challenge, partially due to the lack of a human model system. In this study, we have generated two types of induced pluripotent stem cells (iPSCs) with sialidosis-specific NEU1G227R and NEU1V275A/R347Q mutations (sialidosis-iPSCs), and further differentiated them into neural precursor cells (iNPCs). Characterization of NEU1G227R- and NEU1V275A/R347Q- mutated iNPCs derived from sialidosis-iPSCs (sialidosis-iNPCs) validated that sialidosis-iNPCs faithfully recapitulate key disease-specific phenotypes, including reduced NEU1 activity and impaired lysosomal and autophagic function. In particular, these cells showed defective differentiation into oligodendrocytes and astrocytes, while their neuronal differentiation was not notably affected. Importantly, we found that the phenotypic defects of sialidosis-iNPCs, such as impaired differentiation capacity, could be effectively rescued by the induction of autophagy with rapamycin. Our results demonstrate the first use of a sialidosis-iNPC model with NEU1G227R- and NEU1V275A/R347Q- mutation(s) to study the neurological defects of sialidosis, particularly those related to a defective autophagy–lysosome pathway, and may help accelerate the development of new drugs and therapeutics to combat sialidosis and other LSDs.

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“…18). Nevertheless, iPSC were successfully developed and are valuable tools for personalized medicine approaches, as was demonstrated for single patient variants of sialidosis, 19 CLN5, 20 Gaucher disease (reviewed in Ref. 21), and many others 22–24 .…”

Section: Cell Culture Modelsmentioning

confidence: 99%

Development of precision therapies for rare inborn errors of metabolism: Functional investigations in cell culture models

Didiasova,

Banning,

Tikkanen

2023

J of Inher Metab Disea

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Due to the low number of patients, rare genetic diseases are a special challenge for the development of therapies, especially for diseases that result from numerous, patient‐specific pathogenic variants. Precision medicine makes use of various kinds of molecular information about a specific variant, so that the possibilities for an effective therapy based on the molecular features of the variants can be elucidated. The attention to personalized precision therapies has increased among scientists and clinicians, since the “single drug for all patients” approach does not allow the classification of individuals in subgroups according to the differences in the disease genotype or phenotype. This review article summarizes some approaches of personalized precision medicine that can be used for a cost‐effective and fast development of therapies, even for single patients. We have focused on specific examples on inborn errors of metabolism, with special attention on drug repurposing. Furthermore, we provide an overview of cell culture models that are suitable for precision medicine approaches.

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Generation of human induced pluripotent stem cells (hIPSCs) from sialidosis types I and II patients with pathogenic neuraminidase 1 mutations

Cited by 4 publications

References 5 publications

Safety and biodistribution of exosomes derived from human induced pluripotent stem cells

Safety and biodistribution of exosomes derived from human induced pluripotent stem cells

Modeling Sialidosis with Neural Precursor Cells Derived from Patient-Derived Induced Pluripotent Stem Cells

Development of precision therapies for rare inborn errors of metabolism: Functional investigations in cell culture models

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