Context: In a recent study, scientists have reported successful generation of a live chimaera in non-human primates – species evolutionarily close to humans. This is the first time scientists have succeeded in producing a live infant chimeric monkey.
Genetic Chimaera
- A genetic chimaera is a single organism composed of cells of more than one distinct genotype (or genetic makeup). E.g.,
- In animals:
- Half-sider budgerigar, a type of common parakeet, has different colours on either side of its body due to chimerism.
- Anglerfish displays an extreme degree of symbiotic chimerism in which the male fish fuses with and is eventually absorbed into the female fish, mixing their genetic makeups into a single animal.
- Marine sponges are known to have up to four distinct genotypes in a single organism.
Natural Chimaeras among Humans:
- It can occur when the genetic material in one cell changes and gives rise to a clonal population of cells different from all the other cells.
- Fusion of two fertilised zygotes early in the embryonic stage can also lead to a condition in which two genetic makeups coexist in a single individual.
- Chimerism can also result from twin or multiple pregnancies evolving into a single foetus or a twin foetus being absorbed into a singleton.
- Individuals living with two blood types have been documented. Pregnant women have been known to harbour genetic material of her foetus in the bloodstream during pregnancy.
- Such foetal DNA can be used to screen for genetic defects and congenital abnormalities using non-invasive prenatal testing.
- A phenomenon called microchimerism exists in which traces of the foetus’s genetic material are observed in mothers’ tissues many years after childbirth, resulting in two different genetic materials in a single person.
- Solid organ transplants in humans are bound to produce individuals with two unique genetic makeups as well.
- The makeup of the donor’s organs is significantly different from that of the recipient’s other tissues, resulting in chimerism.
- Bone marrow transplants result in chimeric individuals.
- Individuals undergoing treatments like bone marrow transplants usually have their bone marrow destroyed and replaced by that from a suitable donor.
- Since the donor’s bone marrow contains stem cells, they will produce blood cells that will subsequently repopulate the recipient’s blood-cell repertoire.
- Eventually, the recipient will have blood cells that resemble the donor’s and will be different from the genetic makeup of the recipient’s other tissues – resulting in a chimeric individual.
Chimaeras in Non-human Primates:
- Previously, chimaeras have been induced in laboratory settings, of rat-mouse, human-pig, and human-cow in order to ‘generate’ human organs.
- While rat-mouse chimerics had a near-normal lifespan, human-pig chimaeras had to be terminated in three to four weeks.
- Though such studies have shown promise for growing organs for transplantation, they are limited by the fact that rats, mice, pigs and cows are evolutionarily distant from humans, and will pose biological and technical challenges when being used to grow human organs.
- In a recent landmark study, scientists reported the successful generation of a live chimaera in non-human primates – species that are actually evolutionarily close to humans. This is the first time scientists have succeeded in producing a live infant chimeric monkey.
- The study opens new doors for scientists to use non-human primates to create chimaeras that could become models for basic and translational biomedical applications in the near future.
Applications:
- Human-pig chimaeras have been induced in laboratory settings in a bid to develop model systems that could ‘produce’ human organs of a suitable size, anatomy, and physiology.
- Successful application of animal insulin and the more recent use of animal heart valves in human surgeries have saved human lives.
- Researchers have made attempts to grow full human organs inside the bodies of animals using advancements in induced pluripotent stem cells (iPSCs) technology.
Pluripotent stem cells:
- Pluripotent stem cells hold promise in the field of regenerative medicine. Because they can propagate indefinitely, as well as give rise to every other cell type in the body (such as neurons, heart, pancreatic, and liver cells).
- The most well-known type of pluripotent stem cell is the embryonic stem cell. However, since the generation of embryonic stem cells involves destruction (or at least manipulation) of the pre-implantation stage embryo, there has been much controversy/ethical concerns surrounding their use.
Induced pluripotent stem cells (iPSCs):
- Induced pluripotent stem cells (iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from a somatic cell.
- The iPSC technology was pioneered by Shinya Yamanaka and Kazutoshi Takahashi in Kyoto, Japan, who together showed in 2006 that the introduction of four specific genes, collectively known as Yamanaka factors, could convert somatic cells into pluripotent stem cells.
- Shinya Yamanaka was awarded the 2012 Nobel Prize along with Sir John Gurdon for the discovery that mature cells can be reprogrammed to become pluripotent.
- iPSCs can be differentiated into various cell types, such as neurons, heart cells, and liver cells, allowing researchers to study diseases at the cellular level and develop potential treatments.
- The advantage of iPSCs is that they can be derived directly from a patient’s own cells, eliminating the need for embryonic cells and avoiding issues related to immune rejection.
- While the iPSC technology has not yet advanced to a stage where therapeutic transplants have been deemed safe, iPSCs are readily being used in personalised drug discovery efforts and understand the patient-specific basis of disease.
