Transplantation Of Living Cells, Tissues Or Organs From One Specie To Another. Such Cells, Tissues Or Organs Are Called Xenotransplants.
co-author : Hafsa Ahmed Khan
Possibilities and concerns
Have you ever given thought to the idea that maybe, in the near future we might be able to go organ shopping too. Won’t be as boring as grocery shopping but it’ll definitely be a breakthrough for people who have to wait for months before getting an organ availability for their transplant. Not only will it save thousands of lives, but will definitely increase the average human life span too. But the real question is, is it possible.
From a scientist’s point of view, yes it is possible. And the answer lies within “xenotransplantation”. This long confusing word actually refers to the transplantation of living cells, tissues or organs from one specie to another. Such cells, tissues or organs are called xenografts or xenotransplants. The concept starts with stem cells, cells that have the magical properties to develop into any type of cell of the human body. This property of the stem cells to differentiate into specialized cells is termed as potency. Stem cells can be totipotent, pluripotent, multipotent and so on. Totipotency is the ability of a stem cell to differentiate into any type of cell, pluripotency is the ability to differentiate into cells of the three germ layers namely endoderm, mesoderm and ectoderm while multipotency is the ability to differentiate into different types of cells of a specific kind. Considering pluripotency, scientists started to work on the idea that if these cells can differentiate to make an organ or tissue inside the human body, then they must be able to do so in artificially induced conditions too. From this thought arose the concept of Induced pluripotent stem cells (iPS cells). iPS cells are usually derived from the skin or blood and are induced or in other words “re-programmed” back into embryonic-like pluripotent state that enables the development of an unlimited source of any type of human cell needed for therapeutic purposes. For example, iPS cells can be engineered into becoming beta islet cells to treat diabetes, blood cells to create new blood free of cancer cells for leukemia patients, or neurons to treat neurological disorders. Because of such properties these kinds of cells hold great promise in the field of regenerative medicine. Looking at things from an alternative angle, iPS cells can also be used to give rise to whole organs as their potency enables them to do so. One such experiment has already been done successfully by Takebe et al. They used cells from human skin and engineered them to pluripotent state such that they were able to develop into small liver buds. These liver buds were then implanted into mice and astounding results were observed. The organs developed vascular systems and started performing liver specific functions within weeks. (Takebe et al.,, 2013). These developments which led to the creation of fully functional human organoids from iPS cells were clearly a break through. The next question that arose was that what if there was some way to get iPS cells to develop into human transplantable organs too? Working on this possibility, scientists began experiments which sought to produce human organs in animal chimeras. In simple words, they started working on creating animals that would harbor iPS cells of a specific kind and these cells would in turn develop into whole organs, making the animal a kind of vessel for organs that could be transplanted directly into humans.
The flight of Icarus
In Greek mythology, the story of the flight of Icarus has great importance. In order to achieve his highly ambitious flight, Icarus chimerized his body with the key missing component, wings, which he borrowed from another animal (Rashid et al.,, 2014). Using this idea, animal chimeras were used to harbor the human organs that were to be induced in them. Work started from rodents like mice but since organ size depends on the environment it gets developed in, there was a need to select an animal that had a physiology similar to humans. Many researchers considered pigs as a preferred source for clinical xenotransplantation. This selection was not only due to similar physiology but also because pigs are relatively easier to breed. This can result in a useful feature for rapid development of genetically modified pigs acting as an efficient source of human transplantable organs (Yang et al.,, 2007).
How is it done?
Uptil now a lot of experiments have been performed regarding xenotransplantation. Matsunari et al. worked on creating pigs having human transplantable pancreata. They proved that a functional organ derived from exogenic pluripotent cells can be formed when organogenesis-disabled embryos are complemented by allogenic blastomeres (Matsunari et al.,, 2013). Blastomere is a cell that arises after a cleavage in the zygote after fertilization and is a precursor to blastula formation, blastula being a hollow sphere of cells indicative of the early stages of embryonic development in animals. What “Complementation of organogenesis disabled embryos with allogenic (non identical specie) blastomeres” basically means is that the scientists created apancreatic pigs whose embryos were then complemented with blastomeres containing human pluripotent cells for the organogenesis of human pancreata. These pancreata which were produced from exogenic pluripotent cells were fully functional and normal in their configuration (Matsunari et al.,, 2013). The idea used was that if an empty niche or environment is available in an animal’s body, then iPSC derived cellular progeny can be used for the development of that particular organ in the available space. As human iPSC were used here, the allogeneic blastomere complemented apancreatic pigs gave rise to a progeny containing pacreata that were suitable to be transplanted into humans. The apancreatic pigs created were inturn used as a source of sperms for giving rise to an even larger number of pacreatogenesis disabled embryos. The following figure will help undestand the whole process more clearly.
This technology although has a lot of implications in regenerative medicine and beyond but there are a lot of bioethical concerns that need to be sought out before experimenting in this field. Research that involves the introduction of human DNA sequence into animals, or the mixing of human and animal cells or tissues, to create entities referred to as “animals containing human material”(ACHM) is well established (Rashid et al.,, 2014). Experiments always have certain avenues that although are not the main area of focus but they still play important roles. The possibility of what such undiscovered avenues might be in experiments involving merger of human and animal cells leaves a person thinking about the unthinkable. There are many things that we need to consider prior to working with such tools, like what if the induction of human cells in an animal results in inducing human like cognitive abilities in the animal too. What if human like gametes were to produce from animal chimeras or if the cellular and genetic modifications would lead to animals developing human like phenotypes like skin color, limbs or facial structures or characteristics such as speech. (Any reference to Dawn of the Planet of the Apes is completely coincidental).
The possibilities of using this narrative to explore new grounds of regenerative medicine are basically endless. Scientists have also tried to transplant specific cells instead of whole organs, for instance fetal pig islet cells into human diabetic patients. Similarly, pig neural cells were used for patients with Huntington’s or Parkinson’s disease. An attempt on bone marrow cells transplant was made too, when a person suffering from AIDS received baboon bone marrow cells to boost T cell production but all these cases had no sufficient record of graft survival (2000). Using gene modification, scientists have worked on creating animal donor progenies which will have less expression of antibodies causing xenograft rejection. As the crux of the talk here is basically animal chimeras, one can think of the development of naturally present unique properties of animals in humans. For example, what if we were to take the limb regenerative ability of the epidermal cells of lizards and similar reptiles and xenograft them in humans. What if there was some possibility of getting superior night vision by xenotransplanting rod cells of animals associated with having extremely good night vision? What if the xenotransplants containing muscle fibres of a cheetah gave a human extraordinary speed? The what ifs that could arise here are almost endless and so is the potential of this technology.
Icarus flew too close to the sun and crashed into the sea because his wings which were made of wax could not bear the heat, hence the saying, “Don’t fly too close to the sun” originated. Something on similar patterns needs to be adopted in real scientific world too. Nobody can stop human minds from thinking about unanswered questions or exploring new areas and technologies. But what we can do is understand the limitations and bounderies that come with each discovery. Generating human organs in livestock animals is a dream to any scientist working to imrpove modern medicine, but for now it can be used for toxicology studies and disease/ therapeutic models. With time as the technology and tools progress, there is a need to evolve the safety measures too so that the work on xenotransplantation could be made not only available to all but acceptable by all too. Surely with great power comes great responsibilty.