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Stem cell breakthrough by Wellcome Sanger Institute researchers and colleagues boosts regenerative medicine

A major stem cell breakthrough that has implications for regenerative medicine, organ transplantation, drug screening and our understanding of pregnancy complications has been announced by researchers.

Pig EPSC (expanded potential stem cell) colonies.Images: Xuefei Gao (11972545)
Pig EPSC (expanded potential stem cell) colonies.Images: Xuefei Gao (11972545)

Scientists at Wellcome Sanger Institute and their international colleagues have created human and pig stem cells with greater potency than any derived before.

The Expanded Potential Stem Cells (EPSCs) have the capability of the very first cells in the developing embryo. They retain some ‘totipotency’, meaning they can develop into any type of cell – including those beyond the reach of conventional stem cells.

These existing types have already proved very useful for research into development, modelling disease and developing drugs, but have their limitations.

Dr Xuefei Gao, a first author on the paper from LKS Faculty of Medicine of The University of Hong Kong (HKUMed), and previously from the Wellcome Sanger Institute, explained: “These EPSC stem cells possess developmental potency that is not generally seen in conventional embryonic or induced pluripotent stem cells.

“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 work, published in Nature Cell Biology, represents the first time scientists have been able to derive stem cells from early pig embryos.

This is significant because domestic pigs have great potential for biomedical research, thanks to their genetic and anatomical similarities to humans, including similar organ sizes.

Professor Pentao Liu, the leader of the study, from the School of Biomedical Sciences and Stem Cell and Regenerative Medicine Consortium at HKUMed, and previously from the Wellcome Sanger Institute, said: “Scientists have been attempting to derive porcine embryonic stem cells for decades without much success.

“With our Expanded Potential Stem Cell technology, we have now successfully derived and characterised stem cells from porcine preimplantation embryos. We have also established similar human stem cells. Our study represents a significant advance in stem cell research.”

EPSCs are derived from culturing cells at the earliest stage of development, when the fertilised egg has divided into only four or eight cells.

Pig EPSC (expanded potential stem cell) colonies.Images: Xuefei Gao (11972549)
Pig EPSC (expanded potential stem cell) colonies.Images: Xuefei Gao (11972549)

The group created the first EPSCs in 2017 by targeting key molecular pathways during the very earliest stages of development in mice.

At these stages, cells are like a blank sheet of paper and mammalian species are very similar. Now the researchers have shown the technology can be used to create human and pig EPSCs. The opportunity to genetically modify pig stem cells will also be beneficial for animal health and food production.

Dr Monika Nowak-Imialek, 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. EPSCs’ great potential to develop into any type of cell provides important implications for developmental biology, regenerative medicine, organ transplantation, disease modelling, and screening for drugs.”

Human EPSCs can produce large numbers of placenta cells – called trophoblasts – meaning they offer the opportunity to investigate pregnancy complications such as pre-eclampsia and miscarriages.

Types of stem cell

Pig EPSC (expanded potential stem cell) colonies.Images: Xuefei Gao (11972551)
Pig EPSC (expanded potential stem cell) colonies.Images: Xuefei Gao (11972551)

Existing stem cell types include embryonic stem cells, derived from the inner mass of an early pre-implantation embryo, donated with consent at IVF clinics. They can replicate indefinitely, and turn into each of the 220-plus cell types in the adult body.

This gives them the potential for use in cell therapies - a type of regenerative medicine, whereby they could be used to replace tissue after injury or disease.

Meanwhile, induced pluripotent stem cells (iPSCs) are those reprogrammed back from other cell types - such as skin - into an embryonic stem cell-like state using Nobel Prize-winning technology. These resolve the problem of needing to use embryos, and also give rise to the opportunity to create patient-matched cells: meaning an individual’s own cells could potentially be used in a therapy, avoiding the problem of the immune system rejecting them.

As yet, the technology has not been advanced enough to enable transplants to take place, and there are issues over the speed and reprogramming success of some iPSCs.

The new stem cells, EPSCs, offer advantages in that they can develop into more cell types, including those in the placenta.

The researchers say they represent a “unique cellular platform for translational research in biotechnology and regenerative medicine”.

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