Platform to study intracellular polystyrene nanoplastic pollution and clinical outcomes

Abstract

Increased pollution by plastics has become a serious global environmental problem, but the concerns for human health have been raised after reported presence of microplastics (MPs) and nanoplastics (NPs) in food and beverages. Unfortunately, few studies have investigate the potentially harmful effects of MPs/NPs on early human development and human health. Therefore, we used a new platform to study possible effects of polystyrene NPs (PSNPs) on the transcription profile of preimplantation human embryos and human induced pluripotent stem cells (hiPSCs). Two pluripotency genes, LEFTY1 and LEFTY2, which encode secreted ligands of the transforming growth factor‐beta, were downregulated, while CA4 and OCLM, which are related to eye development, were upregulated in both samples. The gene set enrichment analysis showed that the development of atrioventricular heart valves and the dysfunction of cellular components, including extracellular matrix, were significantly affected after exposure of hiPSCs to PSNPs. Finally, using the HiPathia method, which uncovers disease mechanisms and predicts clinical outcomes, we determined the APOC3 circuit, which is responsible for increased risk for ischemic cardiovascular disease. These results clearly demonstrate that better understanding of NPs bioactivities and its implications for human health is of extreme importance. Thus, the presented platform opens further aspects to study interactions between different environmental and intracellular pollutions with the aim to decipher the mechanism and origin of human diseases.

Nanoplastics as a Potential Environmental Health Factor: From Molecular Interaction to Altered Cellular Function and Human Diseases

“…PS is a thermoplastic polymer characterized by high translucency, durability and may be easily dyed (12). Global polystyrene capacity in 2016 was 14.7 megatons and Europe and North America are, after China, the biggest producers of polystyrene (16.3% and 17%, respectively; https://www.…”

Genome-scale mechanistic modeling of signaling pathways made easy: A bioconductor/cytoscape/web server framework for the analysis of omic data

“…Mechanistic models have successfully been used to understand the disease mechanisms behind different cancers [7] , [8] (including neuroblastoma [9] , [10] and glioblastoma [11] ) rare diseases [12] , [13] , complex diseases such as diabetes [14] or obesity [15] , the mechanisms of action of drugs [16] or gender-specific effects of drugs in cancer [17] . In addition to diseases, other scenarios have been studied, such as the molecular mechanisms of death and the post-mortem ischemia of a tissue [18] or the effects of nanoplastics on embryos and human induced pluripotent stem cells [19] .…”

Special Series: Stem Cells and Hearing Loss

“…most recent research, we proudly introduce this new series, which summarizes the stem cell field's progress focusing on HL. [1][2][3][4][5] In the past 10 years, stem cell technologies have enabled differentiation of human sensory cell types in vitro, providing novel tools to study inner ear development, model disease, and validate various therapeutic approaches. 5 Ethically regulated access to human embryonic and fetal material and human induced pluripotent stem cells (hiPSCs) has allowed the scientific and clinical community to better understand the mechanisms orchestrating normal and abnormal early inner ear development and create conditions for targeted differentiation and genetic editing/manipulation.…”

“…Considering age-related, acoustic, ototoxic, and genetic insults, which are the most frequent causes of irreversible damage of inner ear hair cells and spiral ganglion neurons, 14,15 new methods of genome editing could bring additional opportunities to understand the pathogenesis of HL and identify novel therapies. 3 In this review, Stojkovic et al 3 summarized the CRISPR/Cas9 platform and its potential to accelerate basic and translational research in HL. One of the work's conclusions is that stem cells' usage for therapeutic purposes still faces several significant obstacles, particularly concerning efficiency, efficacy, and safety.…”

“…One of the work's conclusions is that stem cells' usage for therapeutic purposes still faces several significant obstacles, particularly concerning efficiency, efficacy, and safety. 3 Finally, for therapeutic purposes, cultured stem cells must be precisely integrated within their microanatomical niche after being introduced into the inner ear. 5 Whether this will be done via intraperilymphatic or intraendolymphatic injection approach, technical challenges remain, [16][17][18][19][20] Nevertheless, we are confident that the progress achieved in the past decade will unceasingly continue to flourish.…”