Progress towards pig transplants

The creation of stem cells in pigs “could aid research into human disease, and the breeding of animals for organ transplants for humans”, BBC News has said. The website reported that Chinese scientists have developed a method of giving adult pig cells the ability to turn into any tissue in the body, just like cells in an embryo. It is hoped the development could aid human disease research and the use of animal organs for human transplants.

The research behind this story is an important development in stem cell research and provides one of the first insights into the properties of pig embryonic stem cells. This work demonstrates how adult pig cells could be induced to develop into cells that express the characteristics of stem cells in human embryos. These cells can then develop into any type of body cell.

There are many potential roles for reprogrammed pig stem cells. These include investigating disease treatments in genetically modified pigs or producing modified pig organs for transplant, which have a lower risk of being rejected by the body. While this is important work, these possible uses of the research remain some way off.

Where did the story come from?

The research was conducted by Zhao Wu and colleagues from a number of Chinese institutions, including the Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and the Institute of Biochemistry and Cell Biology.

The study received funding from a number of sources, including the Chinese Academy of Sciences Knowledge Creation Program, Shanghai Science and Technology Developmental Foundation and Shanghai Institutes for Biological Sciences. The study was published in the peer-reviewed Journal of Molecular Cell Biology .

What kind of scientific study was this?

This was a laboratory study in pigs that attempted to generate a type of stem cell with the potential to develop into a range of other cell types. This may potentially be used to genetically engineer pigs for scientific and medical purposes.

Pigs have long been of interest in research into human medicine because their organ structure and function are similar to those in humans. While pigs have been involved in a number fields of research, so far only embryonic stem cells from rodents and primates have been firmly established.

The researchers behind this study say that, so far, there has been little success in using the domestic pig to develop “pluripotential cells”, which (like cells in an embryo) have the potential to develop into a range of different cell types. They also say that the characteristics of pig embryonic stem cells, such as their structure, surface markers and pluripotency to develop into other cells, have not yet been documented.

Pluripotential stem cells developed from an animal could have a number of medical uses, including creating genetic models for human diseases and resistance to disease, and developing genetically engineered animals for organ transplantation.

In this laboratory study, the researchers investigated whether they were able to generate a particular type of stem cell, known as porcine-induced pluripotent stem (iPS) cells. These cells have a potential role in genetic engineering. They were generated by taking adult pig cells from the ear and bone marrow and using a virus to introduce “reprogramming” material. After one to two weeks, researchers examined the cells in the laboratory to see whether they had been able to induce the expression of stem cell characteristics.

What were the results of the study?

The researchers demonstrated that the generated pig iPS cells expressed a similar make-up to that of human embryonic stem cells. These cells also:

• expressed a number of specific genes, enzymes and cell surface markers (alkaline phosphatase, SSEA3, SSEA4, Tra-1-60, Tra-1-81, Oct3/4, Nanog, Sox2, Rex1 and CDH1),
• had high activity levels of telomerase, the enzyme controlling telomeres (sections of condensed DNA) and DNA replication, and
• had normal chromosome pairs.

Importantly, the cells were able to differentiate into cell types of all three germ layers that are formed in the developing embryo, a characteristic of pluripotential stem cells. These layers are:

• endoderm, which goes on to develop into the gastrointestinal organs, liver, pancreas and thyroid glands, and the lining of the respiratory system,
• mesoderm, which forms the skeleton, dermis, muscle and connective tissue, heart, blood, lymph and spleen, and urogenital system, and
• ectoderm, which forms the brain and nervous system, eye lens and epidermis.

This ability to differentiate into cell types was observed in the laboratory. The researchers then tested this pluripotency by injecting the iPS cells into genetically engineered mice and observing the formation of a teratoma, a type of cancer made up of tissues representative of all three germ layers.

What interpretations did the researchers draw from these results?

The researchers say that their study has revealed properties of pluripotent stem cells from pigs and that these properties may facilitate the eventual establishment of porcine pluripotential embryonic stem cells. They also say they have shown that induced stem cells could potentially be used to generate pigs with precisely modified genetics.

What does the NHS Knowledge Service make of this study?

Reportedly, embryonic stem cell lines have only been established in rodents and primates, but this research provides one of the first insights into the properties of pig embryonic stem cells, their structure, surface markers and potential to develop into other cell types. These advances will hopefully lead to the establishment of pig stem cell lines in the future.

This work is an important development in the field of stem cell research. It demonstrates how adult pig cells could theoretically be induced to develop into cells which express the characteristics of human embryonic stem cells and could develop into any type of body cell.

There are many potential roles for reprogrammed pig stem cells, such as creating transplantable, modified pig organs with a lower risk of being rejected, or investigating treatments for human disease in genetically modified pigs. However, this is very early research and this type of medical use remains some way off.