13 December 2019

Alien spermatozoa

Donor bone marrow displaced the patient's germ cells

Polina Loseva, N+1

Criminologists have found a man who, after bone marrow transplantation, donor cells replaced not only his blood, but also part of the epithelium of the tongue and cheek, The New York Times reports. In addition, in four years, foreign cells completely displaced the patient's own spermatozoa. Despite the fact that the man feels well and has no plans to have children, his story shows that bone marrow transplantation can lead to unforeseen results, up to mistakes in police investigations.

A person who receives a transplant of any organ – be it skin, kidney or red bone marrow – becomes a chimera: cells of two different genotypes begin to coexist in his tissues. By itself, this neighborhood does not threaten anything, unless there is an immune rejection. In the same case, when the genotypes are similar, as it happens in relatives or carefully selected donor-recipient pairs, cells can peacefully get along side by side for decades.

Natural chimerism occurs, for example, during pregnancy: the mother and the embryo exchange cells, and then they remain in the tissues for a long time. Also, people can become chimeras even before birth if they receive their twin's cells. In most such cases, the percentage of chimerism is low and foreign cells do not manifest themselves in any way, therefore they are invisible if they are not specifically searched for by genetic markers.

When transplanting hematopoietic blood cells, they can displace host cells from the bone marrow completely or partially, but until now it was believed that this does not affect other tissues. The new case shows that in this area the scale of the consequences can be very different.

In 2014, doctors identified the American criminologist Chris Long with acute myeloid leukemia and prescribed a course of chemotherapy, and then transplanted his bone marrow. After that, Long managed to fully recover.

transplant1.jpg

Here and below are shots from the presentation of Long and Romero.

Long's forensic colleagues became interested in the possible consequences of transplantation: they suspected that foreign cells could affect the results of his DNA tests. At the insistence of his colleagues, Long submitted a buccal epithelium sample (scraping from the cheek) before the procedure, and after it, cells were taken from him from other places: blood, cheeks, lips, tongue, hair and sperm.

According to the data that the criminologists received, Long turned out to be a disproportionate chimera: within four months, his blood was completely replaced by donor cells – in this sense, the transplantation was successful. In addition, foreign cells appeared in the tissues of the oral cavity: four years after the bone marrow transplant, nine percent of donor cells appeared in Long's cheek. There were more of them in the epithelium of the tongue and lips: 25 and 34 percent, respectively. Practically no chimeric cells were found in the hair: traces of foreign DNA appeared there only by the fourth year after the procedure. But Long's sperm became 100 percent donor.

transplant2.jpg

It is unknown how the hematopoietic cells managed to spread so extensively throughout the patient's body. Long and his colleagues believe that the cells could have entered the oral cavity together with blood through wounds that appeared there during treatment. The appearance of donor cells in the hair is more difficult to explain: perhaps Long was actively scratching or pulling out his hair at some point.

Finally, it is completely unclear how the blood cells ended up inside the testes. Long's attending physician attributes this to the fact that the man underwent a vasectomy procedure. After that, their own spermatogenesis is suspended, and those cells that are still formed eat macrophages. After chemotherapy, which was performed before transplantation, sperm precursors could die, and hematopoietic cells could take their place. It is also known that under certain conditions, blood stem cells can differentiate in different directions, including into germ cells.

For Long himself, his chimerism will have no consequences. In addition, he is not in danger of having children "from a donor": he has already undergone a vasectomy and no longer plans to have children.

From the editorLong's story makes us think about how safe bone marrow transplantation is in general and how to prevent the birth of "foreign" children after such a procedure.
In addition, criminologists are seriously concerned about these results. Modern DNA genealogy is based on the assumption that every person who gives a DNA sample carries a single genotype. But what if the genotype turns out to be different in different tissues, and in some cases – someone else's? Criminologists are already aware of such cases: for example, a person could be suspected of committing a crime, then it turned out that he was already in prison at that moment, and the perpetrator was his brother, who received donated blood cells. However, until now it was only about blood, but not about other tissues and biological fluids. Now, considering how many people have already entered the genealogical trees that criminologists rely on, there may be even more errors in the investigation if some protocol is not devised to check chimerism.

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