Scientists say they have developed a novel technique to create expanded potential stem cells (EPSCs) of both pig and human cells. These stem cells have the features of the first cells in the developing embryo and can develop into any type of cell, according to the research team from the LKS Faculty of Medicine of The University of Hong Kong (HKUMed), the Wellcome Sanger Institute, and the Friedrich-Loeffler-Institut in Germany.

Their work (“Establishment of porcine and human expanded potential stem cells”), published in Nature Cell Biology, also offers great potential for studying human development and regenerative medicine, they added.

“We recently derived mouse…EPSCs from individual blastomeres by inhibiting the critical molecular pathways that predispose their differentiation. EPSCs had enriched molecular signatures of blastomeres and possessed developmental potency for all embryonic and extra-embryonic cell lineages. Here, we report the derivation of porcine EPSCs, which express key pluripotency genes, are genetically stable, permit genome editing, differentiate to derivatives of the three germ layers in chimeras and produce primordial germ cell-like cells in vitro,” the investigators wrote.

“Under similar conditions, human embryonic stem cells and induced pluripotent stem cells can be converted, or somatic cells directly reprogrammed, to EPSCs that display the molecular and functional attributes reminiscent of porcine EPSCs. Importantly, trophoblast stem-cell-like cells can be generated from both human and porcine EPSCs. Our pathway-inhibition paradigm thus opens an avenue for generating mammalian pluripotent stem cells, and EPSCs present a unique cellular platform for translational research in biotechnology and regenerative medicine.”

The study is the first time scientists have been able to derive stem cells from early pig embryos, noted the scientists. Domestic pigs have a good deal of potential for biomedical research because of their genetic and anatomical similarities to humans, including comparable organ sizes. Being able to genetically-modify pig stem cells will also be beneficial for animal health and food production.

According to Pentao Lin, PhD, the leader of the study from the School of Biomedical Sciences and Stem Cell and Regenerative Medicine Consortium, HKUMed, and previously of the Wellcome Sanger Institute, currently available types of stem cell lines have limitations, and until now it has also not been possible to create embryonic stem cells from pigs and many other farm animals.

“Scientists have been attempting to derive porcine embryonic stem cells for decades without much success,” he said. “With our expanded potential stem cell technology, we have now successfully derived and characterized stem cells from porcine preimplantation embryos. We have also established similar human stem cells. Our study represents a significant advance in stem cell research.”

Since human EPSCs can produce large numbers of trophoblasts, they offer new opportunities to investigate pregnancy complications such as pre-eclampsia and miscarriages.

“These EPSC stem cells possess developmental potency that is not generally seen in conventional embryonic or induced pluripotent stem cells,” explained Xuefei Gao, a first author on the paper from HKUMed, and previously from the Wellcome Sanger Institute. “They have the potential to produce all embryonic and extra-embryonic cell lines—including those in the placenta and yolk sac, turning back the development clock to the very earliest cell type. These cells will enable researchers to study early embryonic development, miscarriage, and developmental disorders.”

The first EPSCs were created in 2017, when the group targeted key molecular pathways during very early development in mice. At these very early embryonic developmental stages, mammalian species are similar and the cells are like a blank sheet of paper. This study has shown that it is possible to use the same approach to create human EPSCs and also to establish EPSCs from pigs.

Monika Nowak-Imialek, Dr. med. vet., an author on the paper from the Friedrich-Loeffler-Institut (FLI) in Germany, said: “Our porcine EPSCs isolated from pig embryos are the first well-characterized pig cell lines worldwide. EPSC’s great potential to develop into any type of cell provides important implications for developmental biology, regenerative medicine, organ transplantation, disease modeling, and screening for drugs.”

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