Potential Threats of Nanoplastic Accumulation in Human Induced Pluripotent Stem Cells

Abstract Background: Micro- and nanoplastics (NPs) produced from the bulk fragmentation are rampant in the world by enormous plastic trash everyday life. NPs can be exposed to humans through a variety of routes, including inhalation and intake. The threat to humans from NPs is increasing invisibly. Nowadays, many people are concerned about human safety and health, but few are reported about the effects of NP on humans. To overcome the limitations in human studies, human induced pluripotent stem cells (hiPSCs) were used as an optimal in vitro platform to investigate developmental toxicology and subtle changes on cellular functions in terms of differentiation potential throughout a long-term culture. Results: Negatively charged polystyrene nanoplastics (PS NPs) were used to exclude acute toxic issues of surface charge and investigate the impact of the NP's size and nature during bioaccumulation. Intracellular observations revealed that NPs up to 1000 nm were over-internalized into single cells within 48 h, and smaller NPs demonstrated greater potency at decreasing number of viable cells by a strong correlation with the number of NPs on an equal mass basis. Also, PS NPs caused a significant reduction in self-renewal capacity of hiPSCs for 48 h. After the cells were exposed to PS NPs for 48 to 96 h at the beginning of the differentiation process, NPs accumulated in hiPSC did not render cellular functions vulnerable or adversely affect EB formation, EB-mediated differentiation, and neural lineage differentiation for up to 14 days.Conclusion: This study confirmed that hiPSC exposure to polystyrene nanoplastics results in acute toxicity and non-significant long-term effects on cellular functions. This report is important for understanding the developmental toxicology of nanoplastics and the origin of disease.

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Using induced pluripotent stem cells to investigate human neuronal phenotypes in 1q21.1 deletion and duplication syndrome

10.1101/2021.02.08.430246 ◽

2021 ◽

Author(s):

Gareth Chapman ◽

Mouhamed Alsaqati ◽

Sharna Lunn ◽

Tanya Singh ◽

Stefanie C Linden ◽

...

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Cortical Neurons ◽

Neuronal Development ◽

Motor Deficits ◽

Differentiation Potential ◽

Induced Pluripotent ◽

The Impact ◽

1Q21.1 Deletion

AbstractCopy Number Variation (CNV) at the 1q21.1 locus is associated with a range of neurodevelopmental and psychiatric disorders in humans, including abnormalities in head size and motor deficits. Yet, the functional consequences of these CNVs (both deletion and duplication) on neuronal development remain unknown. To determine the impact of CNV at the 1q21.1 locus on neuronal development, we generated induced pluripotent stem cells from individuals harbouring 1q21.1 deletion or duplication and differentiated them into functional cortical neurons. We show that neurons with 1q21.1 deletion or duplication display reciprocal phenotype with respect to proliferation, differentiation potential, neuronal maturation, synaptic density, and functional activity. Deletion of the 1q21.1 locus was also associated with an increased expression of lower cortical layer markers. This difference was conserved in the mouse model of 1q21.1 deletion, which displayed altered corticogenesis. Importantly, we show that neurons with 1q21.1 deletion and duplication are associated with differential expression of calcium channels and demonstrate that physiological deficits in neurons with 1q21.1 deletion or duplication can be pharmacologically modulated by targeting Ca2+ channel activity. These findings provide biological insight into the neuropathological mechanism underlying 1q21.1 associated brain disorder and indicate a potential target for therapeutic interventions.

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Using induced pluripotent stem cells to investigate human neuronal phenotypes in 1q21.1 deletion and duplication syndrome

Molecular Psychiatry ◽

10.1038/s41380-021-01182-2 ◽

2021 ◽

Author(s):

Gareth Chapman ◽

Mouhamed Alsaqati ◽

Sharna Lunn ◽

Tanya Singh ◽

Stefanie C. Linden ◽

...

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Cortical Neurons ◽

Neuronal Development ◽

Motor Deficits ◽

Differentiation Potential ◽

Induced Pluripotent ◽

The Impact ◽

1Q21.1 Deletion

AbstractCopy Number Variation (CNV) at the 1q21.1 locus is associated with a range of neurodevelopmental and psychiatric disorders in humans, including abnormalities in head size and motor deficits. Yet, the functional consequences of these CNVs (both deletion and duplication) on neuronal development remain unknown. To determine the impact of CNV at the 1q21.1 locus on neuronal development, we generated induced pluripotent stem cells from individuals harbouring 1q21.1 deletion or duplication and differentiated them into functional cortical neurons. We show that neurons with 1q21.1 deletion or duplication display reciprocal phenotype with respect to proliferation, differentiation potential, neuronal maturation, synaptic density and functional activity. Deletion of the 1q21.1 locus was also associated with an increased expression of lower cortical layer markers. This difference was conserved in the mouse model of 1q21.1 deletion, which displayed altered corticogenesis. Importantly, we show that neurons with 1q21.1 deletion and duplication are associated with differential expression of calcium channels and demonstrate that physiological deficits in neurons with 1q21.1 deletion or duplication can be pharmacologically modulated by targeting Ca2+ channel activity. These findings provide biological insight into the neuropathological mechanism underlying 1q21.1 associated brain disorder and indicate a potential target for therapeutic interventions.

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Increased Neuronal Differentiation Efficiency in High Cell Density-Derived Induced Pluripotent Stem Cells

Stem Cells International ◽

10.1155/2019/2018784 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Sumitra Srimasorn ◽

Matthias Kirsch ◽

Susanne Hallmeyer-Ellgner ◽

Dirk Lindemann ◽

Alexander Storch ◽

...

Keyword(s):

Stem Cells ◽

Neurodegenerative Diseases ◽

Induced Pluripotent Stem Cells ◽

Neuronal Differentiation ◽

Cell Density ◽

Pluripotent Stem Cells ◽

Seeding Density ◽

Differentiation Potential ◽

Neural Lineage ◽

Induced Pluripotent

Human pluripotent stem cells (hPSCs), including induced pluripotent stem cells (iPSCs), provide access to hard-to-obtain cells for studies under physiological and disease conditions. For the study of neurodegenerative diseases, especially sporadic cases where the “disease condition” might be restricted towards the neuroectodermal lineage, obtaining the affected neurons is important to help unravel the underlying molecular mechanism leading to the diseases. Although differentiation of iPSCs to neural lineage allows acquisition of cell types of interest, the technology suffers from low efficiency leading to low yield of neurons. Here, we investigated the potential of adult neuroprogenitor cells (aNPCs) for iPSC derivation and possible confounders such as cell density of infected NPCs on their subsequent neuronal differentiation potential from reprogrammed cells under isogenic conditions. Characterized hiPSCs of defined cell densities generated from aNPCs were subjected to neuronal differentiation on PA6 stromal cells. The results showed that hiPSC clones obtained from low seeding density (iPSC-aNPCLow) differentiated less efficiently compared to those from higher density (iPSC-aNPCHigh). Our findings might help to further improve the yield and quality of neurons for in vitro modelling of neurodegenerative diseases.

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Derivation and Long-Term Culture of Transgene-Free Human Induced Pluripotent Stem Cells on Synthetic Substrates

Stem Cells Translational Medicine ◽

10.5966/sctm.2014-0087 ◽

2014 ◽

Vol 3 (12) ◽

pp. 1410-1417 ◽

Cited By ~ 11

Author(s):

Luis Gerardo Villa-Diaz ◽

Jin Koo Kim ◽

Joerg Lahann ◽

Paul H. Krebsbach

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Long Term Culture ◽

Induced Pluripotent

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Collagen coated electrospun polyethersulfon nanofibers improved insulin producing cells differentiation potential of human induced pluripotent stem cells

Artificial Cells Nanomedicine and Biotechnology ◽

10.1080/21691401.2018.1508031 ◽

2018 ◽

Vol 46 (sup3) ◽

pp. S734-S739 ◽

Cited By ~ 8

Author(s):

Reyhaneh Nassiri Mansour ◽

Fatemeh Soleimanifar ◽

Mohamad Foad Abazari ◽

Sepehr Torabinejad ◽

Abdolreza Ardeshirylajimi ◽

...

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Differentiation Potential ◽

Insulin Producing Cells ◽

Induced Pluripotent

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Ultra-High-Frequency Reprogramming of Individual Long-Term Hematopoietic Stem Cells Yields Low Somatic Variant Induced Pluripotent Stem Cells

Cell Reports ◽

10.1016/j.celrep.2019.02.021 ◽

2019 ◽

Vol 26 (10) ◽

pp. 2580-2592.e7 ◽

Cited By ~ 5

Author(s):

Kai Wang ◽

Anthony K. Guzman ◽

Zi Yan ◽

Shouping Zhang ◽

Michael Y. Hu ◽

...

Keyword(s):

Stem Cells ◽

Hematopoietic Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

High Frequency ◽

Somatic Variant ◽

Hematopoietic Stem ◽

Ultra High Frequency ◽

Induced Pluripotent

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Enhancing cell culture conditions for MPS IIIB induced pluripotent stem cells: The impact of dysregulated heparan sulfate turnover on FGF2 signalling

Molecular Genetics and Metabolism ◽

10.1016/j.ymgme.2019.11.083 ◽

2020 ◽

Vol 129 (2) ◽

pp. S41

Author(s):

Chloe L. Christensen ◽

Francis Choy

Keyword(s):

Stem Cells ◽

Cell Culture ◽

Heparan Sulfate ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Culture Conditions ◽

Induced Pluripotent ◽

The Impact ◽

Cell Culture Conditions

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35. Long-Term Engraftment and In Vivo Selection of Hematopoietic Stem/Progenitor Cells Generated By Vascular Niche Induction of Induced Pluripotent Stem Cells

Molecular Therapy ◽

10.1016/s1525-0016(16)35048-1 ◽

2014 ◽

Vol 22 ◽

pp. S14

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Progenitor Cells ◽

Pluripotent Stem Cells ◽

Hematopoietic Stem ◽

In Vivo Selection ◽

Induced Pluripotent ◽

Selection Of

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283 GENERATION AND CHARACTERIZATION OF BOVINE INDUCED PLURIPOTENT STEM CELLS

Reproduction Fertility and Development ◽

10.1071/rdv25n1ab283 ◽

2013 ◽

Vol 25 (1) ◽

pp. 289

Author(s):

O. J. Koo ◽

H. S. Kwon ◽

D. K. Kwon ◽

K. S. Kang ◽

B. C. Lee ◽

...

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Transgenic Animals ◽

Mouse Embryonic Fibroblast ◽

Embryoid Bodies ◽

Differentiation Potential ◽

Serum Replacement ◽

Induced Pluripotent ◽

Large Animals

Stem cells in large animals are an excellent model for cell therapy research and fine resources for producing transgenic animals. However, there are only few reports of stem cells in large animals because of technical differences between species. In this report, we successfully generate bovine induced pluripotent stem cells (iPSC) using 4 human reprogramming factors (Oct4, Sox2, Klf4, and c-myc) under control of PiggyBac transposition vector. Fibroblasts derived from bovine fetuses were transfected using FugeneHD agent. After 21 days, colony-shaped structures on the culture plates were mechanically detached and then seeded on a mouse embryonic fibroblast (MEF) feeder layer pretreated with mitomycin C. The culture medium was DMEM/F12 supplemented with 20% serum replacement, 5 ng mL–1 basic fibroblast growth factor (bFGF), 0.1 mM β-mercaptoethanol, 1% NEAA, and 1% penicillin-streptomycin antibiotics. The iPSC colonies showed alkaline phosphatase activity and expressed several pluripotency markers (Oct4, Sox2, SSEA1, and SSEA4). To confirm differentiation potential, the iPSC were cultured as embryoid bodies and then plated again. βIII-tubulin (ectoderm) and GFAP or α-SMA (mesoderm) were well expressed on the attached cells. The results revealed that the bovine fibroblasts were well inducted to iPSC that had potential of multilineage differentiation. We hope this technology contributes to improving transgenic cattle production. This study was financially supported by IPET (grant # 109023-05-3-CG000, 111078-03-1-CG000) and the BK21 program for Veterinary Science.

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