(Press-News.org) AUSTRALIAN - LED INTERNATIONAL RESEARCH TEAM GENERATES THE FIRST MODEL OF EARLY HUMAN EMBRYOS FROM SKIN CELLS
In a discovery that will revolutionize research into the causes of early miscarriage, infertility and the study of early human development - an international team of scientists led by Monash University in Melbourne, Australia has generated a model of a human embryo from skin cells.
The team, led by Professor Jose Polo, has successfully reprogrammed these fibroblasts or skin cells into a 3-dimensional cellular structure that is morphologically and molecularly similar to human blastocysts. Called iBlastoids, these can be used to model the biology of early human embryos in the laboratory.
The research, published today (TBC) in Nature, was led by Professor Polo, from Monash University's Biomedicine Discovery Institute and the Australian Regenerative Medicine Institute, and includes first authors Dr. Xiaodong (Ethan) Liu and PhD student Jia Ping Tan, as well as the groups of Australian collaborators Dr. Jennifer Zenker, from Monash University and Professor Ryan Lister from the University of Western Australia and international collaborators, Associate Professor Owen Rackham from Duke-National University of Singapore and Professor Amander Clark from UCLA in the United States.
The achievement is a significant breakthrough for the future study of early human development and infertility. To date, the only way to study these first days has been through the use of difficult to obtain, and scarce, blastocysts obtained from IVF procedures.
"iBlastoids will allow scientists to study the very early steps in human development and some of the causes of infertility, congenital diseases and the impact of toxins and viruses on early embryos - without the use of human blastocysts and, importantly, at an unprecedented scale, accelerating our understanding and the development of new therapies," Professor Polo said.
The Polo Lab succeeded in generating the iBlastoids using a technique called "nuclear reprogramming" which allowed them to change the cellular identity of human skin cells that - when placed in a 3D 'jelly' scaffold known as an extracellular matrix - organised into blastocyst-like structures which they named iBlastoids.
iBlastoids model the overall genetics and architecture of human blastocysts, including an inner cell mass-like structure made up of epiblast-like cells, surrounded by an outer layer of trophectoderm-like cells and a cavity resembling the blastocoel.
In human embryos the epiblast goes on to develop into the embryo proper, while the trophectoderm becomes the placenta. However, "iBlastoids are not completely identical to a blastocyst. For example, early blastocysts are enclosed within the zone pellucida, a membrane derived from the egg that interacts with sperm during the fertilisation process and later disappears. As iBlastoids are derived from adult fibroblasts, they do not possess a zona pellucida" he said.
The lead author on the Nature paper, Dr Xiaodong (Ethan) Liu, a post-doctoral researcher in the Polo Lab, said "only when all the data came together and pointed to the same place, we could believe that we had made such a discovery."
Co-first author and PhD student in the Polo Lab, Jia Ping Tan, added: "we are really amazed that skin cells can be reprogrammed into these 3D cellular structures resembling the blastocyst."
The research is published as the International Society for Stem Cell Research is about to release guidelines for research on modelling human embryos in vitro following 2017 and 2018 reports on the generation of mouse "blastoids" in vitro by the UK and Netherland scientists as well as advances in the generation of human stem cells that replicate aspects of early embryonic development. These guidelines are expected at the beginning of this year.
It is not known whether the new guidelines will reference the study published today in Nature, which is the first to produce an integrated stem cell model that closely mimics key fate and spatio-temporal decisions made by the early human embryo. However, in a paper published in Stem Cell Reports last February (2020), the Society states that: "if such models could be developed for the early human embryo, they would have great potential benefits for understanding early human development, for biomedical science, and for reducing the use of animals and human embryos in research. However, guidelines for the ethical conduct of this line of work are at present not well defined."
Although there is no legislative precedent with respect to working with human integrated stem cell models of blastocysts, such as iBlastoids, all experiments had Monash University Human Ethics approval in compliance with Australian law and international guidelines referencing the "primitive streak rule" that states that human blastocysts cannot be cultured beyond the development of the primitive streak, a transient structure that appears at Day 14 in embryonic development.
Under these legislative recommendations, although iBlastoids are different from blastocysts, the Polo Lab did not culture their iBlastoids beyond Day 11 in vitro and they were monitored closely for the appearance of primitive streak-associated genes.
Infertility and miscarriage can be caused by early-stage human embryos failing to implant or failing to progress at the time of implantation. This takes place in the first 2 weeks after conception when women do not even know they are pregnant. These 'silent' miscarriages are likely to represent a significant proportion of the total number of miscarriages that occur and, according to Professor Polo, the generation of iBlastoids provides a model system that will enable insights into this early stage of pregnancy.
Professor Ross Coppel, the Deputy Dean Research of the Faculty of Medicine at Monash University, noted that this discovery will allow the development of improved methods for IVF, the development of protocols for gene therapy of embryos and better and more informative screening methods for new drugs.
"With further research and the right resources, this discovery could open up entirely new industries for Australia and internationally," he said.
INFORMATION:
The DOI number for this paper will be 10.1038/s41586-021-03372-y. Once the paper has been published online, it will be available at the following URL:
https://dx.doi.org/10.1038/s41586-021-03372-y. This link will go live after the embargo ends.
What The Study Did: Racial and ethnic disparities in very preterm birth and preterm birth among 8,026 women were similar during the first wave of the COVID-19 pandemic in New York City compared with the same period the year prior in this observational study.
Authors: Teresa Janevic, Ph.D., M.P.H., of the Icahn School of Medicine at Mount Sinai in New York, is the corresponding author.
To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/
(doi:10.1001/jamanetworkopen.2021.1816)
Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article ...
Using artificial intelligence and mobile digital microscopy, researchers hope to create screening tools that can detect precursors to cervical cancer in women in resource-limited settings. A study led by researchers at Karolinska Institutet in Sweden now shows that AI screenings of pap smears carried out with portable scanners were comparable to analyses done by pathologists. The results are published in the journal JAMA Network Open.
"Our method enables us to more effectively discover and treat precursors to cervical cancer, especially in low-income countries, where there is a serious lack of skilled pathologists ...
BOSTON - Most surgical patients with a history of penicillin allergy can safely be given the guideline-recommended antibiotic cefazolin to prevent infection instead of several penicillin alternatives that are less effective and more expensive, according to a study conducted by Massachusetts General Hospital (MGH), the University of Colorado Anschutz Medical Campus and the University of Porto in Portugal. The researchers reported in JAMA Surgery that the frequency of allergies to both penicillins and cefazolin was so small that most patients should receive cefazolin regardless of their allergy history.
"Under current practice, ...
UPTON, NY--Electrons in a solid occupy distinct energy bands separated by gaps. Energy band gaps are an electronic "no man's land," an energy range where no electrons are allowed. Now, scientists studying a compound containing iron, tellurium, and selenium have found that an energy band gap opens at a point where two allowed energy bands intersect on the material's surface. They observed this unexpected electronic behavior when they cooled the material and probed its electronic structure with laser light. Their findings, reported in the Proceedings of the National Academy of Sciences, could have implications for future quantum information ...
March 17, 2021 - In recent years, hospital charges and Medicare payments for patients with hip fractures have increased much more rapidly than charges and payments for orthopaedic surgeons, reports a study in the Journal of Orthopaedic Trauma. The journal is published in the Lippincott portfolio by Wolters Kluwer.
The gap in Medicare reimbursements to hospitals compared to surgeons widened substantially in the last decade - even as patient outcomes improved and healthcare resource use decreased, according to a new analysis by Brian Werner, MD, and colleagues of UVA Health, Charlottesville, Va. "The results confirm our hypothesis that hospital charges and payments contribute significantly more to the increasing cost of treating a hip fracture patient than surgeon ...
He and his research group have found a way to more precisely determine the properties of these materials, because they can better account for the underlying disorder. Their article has been designated "ACS Editors' Choice" by the editors of the American Chemical Society journals, who recognise the "importance to the global scientific community" of the Leipzig researchers' work and see it as a breakthrough in the accurate description of phase transition phenomena in disordered porous materials.
In mesoporous materials, the pore openings are far smaller than in a normal sponge: their diameters range from 2 to 50 nanometres and are invisible to the naked eye. Nevertheless, they have a number of interesting properties, including with ...
The abundance and other characteristics of rocks partially extending above the water surface could be important for improving the recovery of aquatic insect populations in restored streams.
Nearly three quarters of stream insects reproduce on large rocks that sit above the water surface by crawling underneath to attach their eggs. Increasing the number of large and stable emergent rocks in streams could provide more egg-laying habitat and allow insects to quickly repopulate restored streams.
"We found that restored streams had fewer emergent rocks for egg-laying and fewer total eggs than naturally intact streams," says Samantha Jordt, first author of the paper and an M.Sc. student at NC State's Department of Applied Ecology.
The study also ...
Simple systems can reproduce faster than complex ones. So, how can the complexity of life have arisen from simple chemical beginnings? Starting with a simple system of self-replicating fibres, chemists at the University of Groningen have discovered that upon introducing a molecule that attacks the replicators, the more complex structures have an advantage. This system shows the way forward in elucidating how life can originate from lifeless matter. The results were published on 10 March in the journal Angewandte Chemie.
The road to answering the question of how life originated is guarded by Spiegelman's monster, named after the American molecular biologist Sol Spiegelman, who some 55 years ago ...
Many people who embrace social welfare programs vote against their own interests, according to new UC Riverside research.
The mitigating factor is education: The more education one has, the more likely one is to stick to one's policy preferences.
"It means candidates who employ tactics such as fear and attaching patriotism to certain concepts can persuade people to vote for candidates who are in opposition to their social beliefs," Diogo Ferrari, a professor of political science at UC Riverside, wrote in his recently published paper, "Education, Belief Structures, Support for Welfare Polices, and Vote," published in the journal Education & Society.
For the study, Ferrari looked at public opinion ...
Brazilian researchers have published a systematic review of the scientific literature showing that some warm-up strategies such as dynamic stretching can effectively prepare soccer players to maintain kicking accuracy, whereas intense physical exercises have a negative effect on the velocity of the ball when kicked, and consumption of carbohydrate beverages during a match can enable players to maintain adequate kicking performance in the concluding moments of prolonged physical exercise such as a sudden-death playoff.
The review, published in the journal Sports Medicine in December 2020, ...
