User:Pearbrownies/Human Chimerism

Human chimerism is a condition characterized by the presence of cells from two or more unique

The term chimera originates from ancient Greek mythology, describing a mythical creature combining features of a lion head, goat body and serpent tail.^[5] Chimeras have become part of contemporary scientific and medical discourse, particularly within the fields of biology and genetics, dating back nearly seven decades ago.^[2] In the scientific context, human chimeras represent entities composed of cells from different sources. Once considered rare, recent research indicates human chimeras are more prevalent than previously believed.^[6] This is due to the challenges in detection when natural human chimeras exhibit entirely normal phenotypes, necessitating genetic testing to reveal underlying differences.^[2]

Natural human chimeras

Natural human chimeras are humans who are born with cell populations from more than one zygote.^[6] Majority of cases of naturally-occurring chimeras have previously gone undetected, especially for chimeras with zygotes of the same sex. However, greater public attention and recent developments in genomic technologies have contributed to increasing identification of this phenomenon.^[7] Natural human chimerism occurs through several means and can be categorized into three groups: microchimerism, fusion chimerism and twin chimerism.^[6][7]

Microchimeras

Microchimerism is the presence of a minor cell population accounting for <1% of the total cell population in an individual.^[3] This small number of cells is distinct from the host’s cells and derived from a different individual. Microchimerism has been observed to arise during pregnancy. The process of microchimerism can occur bidirectionally, creating microchimerism in both the mother or child. This is known as fetal microchimerism and maternal microchimerism respectively.^[6][7] The bidirectional transfer of maternal and fetal cells is asymmetrical,^[8] where a larger number of fetal cells are transferred from mother to child.

Fetal microchimerism, the most common form of natural human chimerism,^[7] involves fetal cells crossing the placenta and integrating into maternal organs. The persistence of fetal cells in the mother's body postpartum has been found to last up to 27 years.^[6][7][9] Maternal microchimerism is the transfer of maternal cells into the fetus, which persists throughout childhood and adult life.^[9]

Fetomaternal microchimerism and the presence of fetal cells in pregnant women have been utilized in the development of the non-invasive prenatal test (NIPT). This diagnostic test utilizes cell-free fetal DNA (cffDNA) in maternal blood to screen for genetic diseases and abnormalities during pregnancy.^[6][7][10]

Fusion chimeras

Fusion chimerism involves the fusion of two or more zygotes in an early embryonic state.^[6][7] This results in an individual containing cell lineages from both zygotes. Fusion chimerism differs from mosaicism, where multiple distinct cell lines arise from a single zygote due to genetic mutations.^[11]

Various mechanisms for fusion chimeras have been proposed, including

Phenotypic traits of chimerism can include a variation of skin pigmentation and iris color. However, there is a lack of readily observable phenotypic characteristics in fusion chimeras which would indicate the chimeric nature of the individual.^[7]

Various quantitative techniques have been utilized for the identification of natural human chimeras. Many cases of natural chimerism have been serendipitously discovered through various tests such as blood group typing.^[6] The primary qualitative methods include blood group typing, karyotyping, polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH).

Blood typing

Natural human chimerism was first identified through routine

Fluorescence in situ hybridization (FISH) is a cytogenetics technique that localizes donor cells at the individual cell level in the background of host cells. This technique employs labeled nucleotide probes that hybridize with specific genomic sequences, allowing the detection of fluorescent signals.^[8] FISH is used in chimerism biology to identify the localization of non-host cells within tissue samples.^[8]

Artificial human chimeras

Man-made chimeras

Man-made or “therapeutic” human chimeras arise from tissue or organ transplants, leading to the presence of two or more blood or tissue donor populations in the recipient's body.^[1] This condition creates an environment where donor and recipient cells from transplantation compete to survive, potentially resulting in one cell population outcompeting another over time.^[1]

Xenotransplant chimeras

Xenogeneic transplant is a procedure that involves the infusion of non-human animal sources into live human cells, tissues or organs, creating a human-animal xenotransplant chimera.^[1][18] For example, an interspecies chimera such as a human-pig chimera can be created by generating humanized hearts in humans from gene-edited pigs. This same technology would apply to other organ sources for transplantation.^[19]

Iatrogenic transplant chimeras

Iatrogenic transplant chimeras arise from an unintended allogeneic transplantation.^[1] It is commonly observed in multiply-transfused trauma patients who require a significant amount of blood transfusion.^[20][21] Research indicates that these types of patients would accept donor granulocytes and lymphocytes despite leukoreduction.^[22] The donated cells are thus able to persist for decades and become “transfusion-associated microchimeras”.^[22]

IVF chimeras

IVF-associated chimeras are created through assisted reproductive technologies known as in vitro fertilization (IVF). During IVF, two or more embryos are transferred into one uterus to increase the chance of successful pregnancy.^[1]

During IVF, the human oocyte is carefully selected from the follicle in the ovary to be fertilized. Next, the chosen oocyte is fertilized with sperms that have been prepared.^[1] Finally, two or more fertilized embryos are implanted into the uterus endometrium within five days post-fertilization.^[23]

The consequence of IVF is the increased likelihood of monozygotic and dizygotic twinning, leading to IVF chimeras also known as twin chimeras. Another potential chimeric outcome is “singletons”, which refers to fusion chimeras or surviving twin chimeras that acquire genetic material from a sibling that perished in the uterus. This is known as the “vanishing twin syndrome”, where the vanished twin disappears in utero.^[1][24] This phenomenon can also be examined in postpartum with the placenta as evidence of the “vanished twin”.

Identification

The methods for the identification of artificial human chimeras are similar to those used for natural human chimeras, though qualitative methods are insufficient.

Ethical considerations surrounding human chimerism predominantly revolve around cases of artificial human chimerism. The earliest discussions of bioethical issues stem from xenotransplantation practices. This procedure involves the transplantation of non-human animal cells, tissues or organs into humans.^[26] Concerns include the harm inflicted upon the donor and the potential health risks posed to the recipient. Proponents argue from a moral standpoint that such practices are beneficial, offering a means to alleviate human organ shortage by utilizing non-human animals as organ sources to save human lives.^[27] However, ethical dilemmas arise due to the risks to human health posed by the xenogenic transplant procedures, alongside concerns for animal welfare and challenges related to obtaining informed consent.^[26]

References