Achieving a world first, scientists in China have induced cells from pigs to become pluripotent stem cells, which like embryonic stem cells are able to develop into any cell of the body.

The study, which is to published early June in the newly launched Journal of Molecular Cell Biology, was the work of principal investigator Dr Lei Xiao, who leads the stem cell lab at the Shanghai Institute of Biochemistry and Cell Biology, and colleagues.

This is the first time anyone in the world has made pluripotent stem cells from somatic cells (as opposed to germline cells such as sperm and eggs) from an ungulate (an animal that has hooves).

The researchers hope this opens the door to making human disease models, engineering animals as sources of organs for transplant into humans, and developing pigs that are resistant to diseases like swine flu.

Quoted in a separate statement, Xiao said:

“Pig pluripotent stem cells would be useful in a number of ways, such as precisely engineering transgenic animals for organ transplantation therapies.”

“The pig species is significantly similar to humans in its form and function, and the organ dimensions are largely similar to human organs,” added Xiao.

Xiao and colleagues took cells from the ears and bone marrow of pigs and using transcription factors introduced by a virus they reprogrammed them and coaxed them to develop into colonies of induced pluripotent stem cells (iPS cells) which are very similar to embryonic stem cells, regarded as the “gold standard” of stem cell research.

Further tests showed that like embryonic stem cells, the new iPS pig cells were capable of differentiating into the types of cells that form the endoderm, mesoderm and ectoderm layers of an embryo.

Working with iPS cells in this way also gives information that should make it easier to develop embryonic stem cells (ES cells) from pig or other ungulate embryos, said the researchers.

“We could use embryonic stem cells or induced stem cells to modify the immune-related genes in the pig to make the pig organ compatible to the human immune system,” explained Xiao, adding that the pigs could then be used as organ donors for human patients without their immune system having an adverse reaction.

Another application could be to create models for human diseases, for many of them are caused by a disorder of gene expression.

“We could modify the pig gene in the stem cells and generate pigs carrying the same gene disorder so that they would have a similar syndrome to that seen in human patients,” explained Xiao, adding that it would then be possible to use the pig model to develop treatments.

And another use could be to breed gene-modified pigs with resistance to diseases like swine flu.

“We would do this by first, finding a gene that has anti-swine flu activity, or inhibits the proliferation of the swine flu virus; second, we can introduce this gene to the pig via pluripotent stem cells, a process known as gene knock-in,” said Xiao.

Another way they could make pigs resistant to swine flu would be to knock out the pig cell membrane receptor that the virus uses to gain access to cells. Doing this would stop the virus invading cells and using their contents to replicate itself.

“We could knock out this receptor in the pig via gene targeting in the pig induced pluripotent stem cell,” explained Xiao.

There could also be applications to farming, not only by helping to breed healthier and more disease resistant pigs, but also by improving the way that pigs grow.

However Xiao warned that it will be several years before this new method moves from the research lab into the clinic.

“Generation of pig induced pluripotent stem cells with a drug-inducible system.”
Zhao Wu, Jijun Chen, Jiangtao Ren, Lei Bao, Jing Liao, Chun Cui, Linjun Rao, Hui Li, Yijun Gu, Huiming Dai, Hui Zhu, Xiaokun Teng, Lu Cheng, and Lei Xiao.
Journal of Molecular Cell Biology, doi:10.1093/jmcb/mjp003
A PDF of the full paper is available at http://www.oxfordjournals.org/our_journals/jmcb/mjp003.pdf.

Sources: Oxford University Press, Comtex/M2 PressWIRE.

Written by: Catharine Paddock, PhD