Plastic production and pollution has become the scourge of our society and our environment. Innumerable global attempts have been made to change this tendency by increasing the risk awareness toward consumers. However, since mid-nineteens, the worldwide production and consumption of plastic has grown excessively over the years, has reached more than 350 million tons1 yearly, while being poorly degraded, and has created a major global challenge. More critically, studies reporting the presence of produced or degraded microplastics (MPs, with a diameter less than 1 mm) and nanoplastics (NPs, with a diameter less than 100 nm) items in food, beverages, sea, air, plants, sea salt, sugar and honey, mineral water, in baby toys and even in human placenta and stool2 have raised concerns about the potential risks and damages that consumption of plastic could have on human health. Polystyrene (PS) is one of the most used and consumed plastic-type for food and beverages packaging including tea and coffee disposable cups, and is also present in material such as dental sealants and used by many professionals including those working in construction. Unfortunately, very little is known about the health effects of microscopic-sized plastic items exposure in humans and very few published data3,4 support the potential detrimental effects of MPs and NPs such as PS items. Moreover, these studies, mostly performed in models such as cultured animal epithelial cells and embryos as well as human somatic and cancer cells, do not identify the biological signaling pathways affected by plastic pollution and their implication in human development and health.
Using pluripotent stem cells of human origin to study the detrimental effect of microscopic plastic items on human health
Recently, a new study5 published in Stem Cells last December and led by the team of ProfMiodrag Stojkovic, (the SPEBO Medical Fertility Clinic in Leskovac, Serbia and Harvard Medical School in Boston) took the advantage of human pluripotent stem cell models4 and developed a human embryo- and stem cell-based platform to test the effect of intracellular pollution on the expression of key genes and biological pathways for human development and predict the related diseases.
As a reminder, human pluripotent stem cells, which include human embryonic stem cells and human induced pluripotent stem cells (derived from genetically reprogrammed somatic cells) used in the present work, are capable of becoming almost any cell or tissue in the human body and can self-renew6,7, both depending on the environmental conditions into which they are placed. More than a decade ago, they emerged as a suitable new model that offers unique advantages to investigate developmental processes in a culture dish, including cell fate, early physiological and pathophysiological development, aging and diseases such as infertility8. Their culturing and utilization hold great promise for both present and future of regenerative medicine, especially in cell replacement therapies. As such, human pluripotent stem cells represent also an excellent model to study human development and diseases that can emerge due to plastic pollution and allows to eventually defining the link between environmental and intracellular pollution5,8.
Exposure of human stem cells models to PS nanosized items leads to altered pluripotency and genotoxicity
By combining the use of these models with new generation RNA sequencing for transcription profile and bioinformatics tools, ProfStojkovic’ s team’s efforts5 led to the discovery that exposure of both pre-implantation human embryos (or expanded blastocyts) and human induced pluripotent stem cells to industrial PS nanosized particles, reduced genes involved in pluripotency as well as embryo implantation (specifically LEFTY1 and LEFTY2 genes) and increased others implicated in eye development (including CA4 and OCLM). Looking at gene set enrichment analysis (defining the groups of genes that are either enriched or depleted and that are functionally related) in induced pluripotent stem cell model, the scientists found out that biological processes including heart valve development, extracellular matrix and cytoskeletal dynamic were affected by intracellular PS pollution. Mechanistically, the team discovered that PS nanosized items exposure in induced pluripotent stem cells leads to an alteration in the signaling pathways playing an important role in fat metabolism. Indeed, by using a mathematical method allowing detection of disease mechanisms and predictions for clinical outcomes, the scientists discovered the alteration of several signaling circuits, including the one implicating the gene APOE3, which is tightly associated with an increased risk for developing ischemic cardiovascular disease.
Studying intracellular pollution in human stem cells: a great promise for human health research.
For the first time, scientists have shown that industrial nanoplastic items such as polystyrene, affect gene expression, reduce the potency of human embryonic and human stem cell models to develop normally and induce processes associated with cellular stress, while increasing the risk for disease development. By providing the importance of understanding the bioactivity of the microscopic plastic items inside the cell, the study has perspectives of huge importance for human health research: “In addition to plastic pollution, the platform can be used to probe the risks associated with other pollutants and contaminants, and can also serve to test combinations of both, for example Cadmium or Polyvinyl Chloride (PVC) plastic, that are present in children’s toys9 or bisphenol A that is already known to be an endocrine disruptor” says Prof. Stojkovic.
Take home message
In addition to the ecological challenges that they induce, the worldwide excessive production and consumption of plastic and its slow degradation can also have implications in human health and development but the risk due to plastic exposure is still not measured properly. In a recent beautiful study, scientists have, for the first time, proposed to use human pluripotent stem cells as a model to study the detrimental effects of microscopic plastic items such as polystyrene (PS), which is part of our every-day plastic consumption. Human pluripotent stem cells have the capacity to become almost any cell or tissue in the human body while being stimulated by different environmental factors and are used in cell replacement therapies such as bone marrow transplants of blood stem cells to treat certain types of cancer. In their study, firmly engaged in a battle against plastic pollution, the stem cells biologist ProfStojkovic and his collaborators discovered that nanosized PS particles exposure in human embryonic and human stems cells shows a reduction in their function, leads to toxic effects on the genes important for key cellular pathways, thus enormously affecting normal cell development. These genes are associated with eye development, cardiac defects and cardiovascular diseases. This study, behind which an enormous work has been performed and has yet to come, opens up a fantastic field of perspectives that enables to specifically dissect and understand the effects of every-day consumed plastic products in the human body, cells by cells, tissue by tissue, organ by organ from infancy to adult age.
A special thank to Prof. Miodrag Stojkovic with whom I shared a great and stimulating discussion on this particularly important subject.
- Heidbreder LM, Bablok I, Drews S, Menzel C (2019). Tackling the plastic problem: A review on perceptions, behaviors, and interventions. Sci Total Environ: 668:1077-1093
- Schwabl, P, Koppel, S., Konigshofer, P, Bucsics, T, Trauner, M, Reiberger, T, Liebmann, B (2019). Detection of various microplastics in human stool: a prospective case series. AnnInternMed. 171: 453e457
- Rahman A, Sarkar A, Yadav OP, Achari G, Slobodnik J (2020). Potential human health risks due to environmental exposure to nano-and microplastics and knowledge gaps: a review. Sci Total Environ 757:143872
- Barbato, V, Talevi, R, Gualtieri, R, Pallotta, MM, Di Nardo, M, Costanzo, V, Catapano, G, Capriglione, T (2020). Polystyrene nanoparticles may affect cell mitosis and compromise early embryo development in mammals. Theriogenology 145: 18e23
- Bojic S, Falco MM, Stojkovic P, Ljujic B, Gazdic Jankovic M, Armstrong L, Markovic N, Dopazo J, Lako M, Bauer R, Stojkovic M (2020). Platform to study intracellular polystyren nanoplastic pollution and clinical outcomes. Stem Cells 38(10):1321-1325
- Zhu Z, Huangfu D (2013). Human pluripotent stem cells: an emerging model in developmental biology. Development 140 : 705-717
- Zakrzewski W, Dobrzynski M, Szymonowicz M, Rybak Z (2019). Stem cells: past, present, and future. Stem Cell Research and Therapy 10: Article number 68.
- Stojkovic M, Stojkovic P, Stankovic K (2020). Human pluripotent stem cells as a unique tools to decipher the effects of environmental and intracellular plastic pollution on human health. Environnemental Pollution 269: 116144
- Turner A (2018). Concentrations and migratabilities of hazardous elements in second-hand children’s plastic toys. Environ Sci Technol, 52 : 3110-3116