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The signals have been restored, thanks to the pig

Transgenic pig cells were transplanted into rats and restored their damaged spines

By Marit Selvin
Cell transplantation as a means of healing has recently begun to be studied in the context of a variety of diseases, including diabetes and Parkinson's. The great progress in this field, along with the severe shortage of organs for transplantation in the world, raises the need for cells suitable for transplantation.

The best source of cells for transplantation is the human body itself. In this case, cells are taken from one place in the body and transplanted in another place (alternatively, cells from the same match can be used). Another option is to transplant cells from another person. Here it is necessary to overcome the problem of rejection. One of the promising options that has recently been tested in many laboratories around the world is the transplantation of embryonic stem cells, cells preserved in an embryonic state and capable of developing into a wide variety of tissues.

The third option is to transplant cells and organs from animals. Today, most scientists agree that the most suitable animal for this purpose is the pig, and many research centers are testing whether it is indeed possible to transplant pig cells into humans. The pigs are easy to breed, and they can be genetically modified to get a better fit for humans. Large pharmaceutical companies have established pig farms with the aim of developing pig breeds that will be used for cell and organ donation.

An important step in this direction was taken by a group of researchers from the United States, led by Jeffrey Koksis from Yale University, who managed to completely restore the transmission of nerve signals in the damaged spinal column of rats by transplanting pig nerve cells. The researchers' findings were published in the September issue of the journal "Biotechnology Nature".

The main problem with transplants is the rejection of the transplanted cells by the recipient body. It can be overcome with drugs that suppress the immune system, but with pig transplants there is another problem: humans and rats naturally have antibodies directed against one of the biochemical components in the pig's cell wall. The binding of the antibodies to this component immediately prevents the graft from being accepted. Researchers know that the first step to implementing a successful pig transplant will require solving this problem.

The researchers from Yale University were able to overcome the problem by injecting into the fertilized eggs of pigs a human gene that encodes a protein, which suppresses one of the main components involved in the process of creating antibodies. All the pigs that developed from the fertilized eggs carried in their genome the human gene, which prevents the strong immune response against the pig cells.

From the transgenic pigs, the researchers collected special cells, which wrap the nerve fibers in the olfactory lobe and enable rapid transmission of nerve signals. Cells support the nerve cells in the nose by causing regrowth of the nerve fibers in damaged places. It is known that if they are transplanted from rat to rat, they support nerve fibers not only in the olfactory lobe but also in other places, where they produce an insulating sheath called myelin around the nerve fibers. The researchers knew that these cells carry a promising potential for transplantation: in several experiments it became clear that when they were transplanted into damaged areas of the central nervous system, they settled in the transplanted area in an orderly manner and stimulated the regeneration of nerve fibers in the spine and brain.

Now, with the appropriate cells in hand, the researchers proceeded to perform the experiment. They cut the sensory part of the spinal cord in ten rats, whose immune system was suppressed (to prevent rejection), and injected the transgenic pig cells into the infected area. A month later, they removed the spinal cord from the rats and checked whether an electric current passed through it stimulates the transmission of nerve signals in the damaged nerve fibers.

The results showed that the transgenic pig cells transplanted into rats caused the regeneration of the sensory pathways. Many nerve fibers grew at the site of the injury, and they transmitted nerve signals even faster than normal fibers. When they examined the area under a microscope, they saw that the transplanted pig cells migrated to the damaged areas and formed isolated myelin sheaths around the regenerated nerve fibers. The researchers note that the transplanted pig cells behaved exactly like cells that are transplanted from rat to rat.

In an accompanying article in the newspaper, the Swedish neurobiologist Lars Olsson notes that the main importance of the research is the possibility of transferring cells from a pig to rats without them being immediately rejected, which raises the possibility that this could also be done in humans. This option could help in the future in transplanting organs such as heart, kidneys, lungs and liver. "What was unthinkable just a decade or two ago has now turned out to be a restorative treatment for an injured spinal cord within reach," writes Olson. At the same time, Olson emphasizes that there are still many obstacles on the way to implementing the method. The rejection must be overcome in the long term, and for this purpose further engineering of the pig cells will be necessary. In addition, the pig cells carry viruses inside them, which can attack human cells, and this will also have to be overcome.
{Appeared in Haaretz newspaper, 13/9/2000}

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