Salk Institute and Chinese researchers report creating a new kind of stem cell, one that is more versatile than any other normally grown in the lab.

Called an extended pluripotent stem cell, it can give rise to every cell type in the body, the researchers say in a recent study. This includes the extra-embryonic tissues such as the placenta that support the developing baby. Just one cell can generate a complete organism.

Embryonic stem cells and artificial embryonic stem cells called induced pluripotent stem cells cant make these extra-embryonic tissues. So neither embryonic nor IPS cells can give rise to a complete embryo, because the supportive tissues necessary for an embryo to survive arent there.

But the extended pluripotent stem cells can reliably give rise to both types of cells, and thus whole embryos and offspring, the scientists report.

The EPS cells were made from human and mouse embryonic stem cells. In addition, they were produced from skin cells, or fibroblasts by treating them with a chemical cocktail. IPS cells, invented in 2006, are generated from fibroblasts by a similar reprogramming process.

Use of IPS cells is regarded as morally acceptable by those who oppose use of human embryonic stem cells, because they cant form an entire embryo. This is the reasoning of the Catholic Church. But since the EPS cells can make whole embryos, at least in mice, how the church will react is unclear.

To demonstrate this ability to make all cell types, the researchers grew an entire mouse from just one EPS cell. They also grew chimeric mice, with human EPS cells integrating into the mice better than embryonic stem cells did.

The study on these new stem cells was published April 6 in the journal Cell. It can be found at j.mp/extendedstem.

Better tool

That characteristic of creating every cell in the body, called totipotency, is normally found only at the very beginning of embryonic development. Embryonic stem cells are usually extracted too late, when the cells have already divided into the embryonic and extra-embryonic lineages.

Totipotent stem cells have been observed in the lab, but they lasted briefly, and didnt yield stable totipotent cell lines.

Salk Institute stem cell researcher Juan Carlos Izpisa Bemonte was a cosenior author of the paper along with Hongkui Deng of Peking University in Beijing. The first authors were Yang Yang, Bei Liu, Jun Xu, and Jinlin Wang; all of Peking University, and Jun Wu, of the Salk Institute.

EPS cell lines provide a useful cellular tool for gaining a better molecular understanding of initial cell fate commitments and generating new animal models to investigate basic questions concerning development of the placenta, yolk sac, and embryo proper, the study stated.

Furthermore, they also provide an unlimited cell resource and hold great potential for in vivo disease modeling, in vivo drug discovery, and in vivo tissue generation in the future. Finally, our study opens a path toward capturing stem cells with intra- and/or inter-species bi-potent chimeric competency from a variety of other mammalian species.

Organs for transplant

The creation of chimeric mice is part of Izpisa Bemontes longstanding goal of growing human organs in animals for transplant.

While mice are too small to grow organs for transplant, they serve as a model to understand how cells from a different species, can be grown in a host body. In this new study, the mice served as a model of how well the EPS cells can integrate.

Izpisa Bemonte is now working to translate his research on chimeric mice to pigs, which are large enough to provide human organs. In January, a team he led reported on work with human-pig chimeras, which were not allowed to grow past the embryonic stage. They also created rat-mice chimeras.

The superior chimeric competency of both human and mouse EPS cells is advantageous in applications such as the generation of transgenic animal models and the production of replacement organs, Wu said in a Salk statement. We are now testing to see whether human EPS cells are more efficient in chimeric contribution to pigs, whose organ size and physiology are closer to humans.

We believe that the derivation of a stable stem cell line with totipotent-like features will have a broad and resounding impact on the stem cell field, Izpisua Belmonte said in the statement.

The work was funded by a number of sources. They include: the National Key Research and Development Program of China; the National Natural Science Foundation of China; the Guangdong Innovative and Entrepreneurial Research Team Program; the Science and Technology Planning Project of Guangdong Province, China; the Science and Technology Program of Guangzhou, China; the Ministry of Education of China (111 Project); the BeiHao Stem Cell and Q9 Regenerative Medicine Translational Research Institute; the Joint Institute of Peking University Health Science Center; University of Michigan Health System; Peking-Tsinghua Center for Life Sciences; the National Science and Technology Support Project; the CAS Key Technology Talent Program; the G. Harold and Leila Y. Mathers Charitable Foundation; and The Moxie Foundation.

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