Commentary on More Drastic Scenarios of Partial Brain and Full Body Replacement
Is outright replacement of tissues a viable option for the treatment of aging? There are factions within the longevity-interested community who think that the paths to either (a) engineering replacement brain tissue for parts of the brain not involved in memory, or (b) transplantation of an old head onto a young body or brain into a young body, are short enough to be worth pursuing, where "short enough" means a few decades of work given sufficient funding. To my mind, major surgery of the sort implied by replacement of large sections of tissue or entire organs is something to be avoided in later life, given the risks and cost. It is better to pursue a strategy of introducing new stem cells or repairing existing cell populations, a more gentle approach that would avoid the need for surgery, and at this point doesn't seem to require a much longer timeline for development.
Brain or cerebral organoids are very specific neuronal cell cultures that were developed from human-induced pluripotent stem cell cultures, but with a slightly modified protocol. Grown spheroids of pluripotent stem cell cultures can be integrated within special solubilized membrane matrices which can support growing cells in a 3D environment, hence, producing organoids. Several scientific publications have already successfully shown that such cerebral organoid cultures present diverse populations of neurons and display processes like cortical development and cell migration. They also excrete their own extracellular matrix with many physiologically relevant components like hyaluronic acid, proteoglycans, and various functional enzymes.
Human embryonic stem cell-derived brain organoids have been implemented with needles into the damaged brain parts of cortical impact-modeled severe combined immunodeficient mice. Grafted organoids not only survived, but also differentiated, showed electroactivity, and extended long signal projections. Moreover, they promoted brain tissue repair and vascularization, learning and memory ability, and reduced glial scarring. The study also raised more questions, like how far the transplanted grafts can go in terms of repairing traumatic brain damage and scarring, as well as how to improve the survival of these neural stem cells in the brain in the future.
Since 2012, there have been some efforts regarding brain transplantation in mice models. A Chinese orthopedic surgeon, famous for being a part of the team that successfully performed the first hand transplant, tried to graft a mouse's head onto another mouse, and the grafted heads survived for about half a year. Somewhere around the same time, an Italian brain surgeon published the protocol that claimed it would make human head transplantation possible. A later review discussed various protective strategies in head transplantation, as well as several protocols to keep the vascular systems connected and brains under hypothermia.
In 2017, further work took place on a cross-circulated bicephalic model of head transplantation to study the long-term effects of transplant rejection and blood flow restrictions during the head transference phase. By using vascular grafts, they connected the thoracic aorta and the superior vena cava from one rat to the carotid artery and extracorporeal veins of another rat. A third rat was used as a blood reservoir and its carotid artery and extracranial vein were connected to the donor rat with silicone tubes before the thoracotomy was performed on the donor rat. A pump and a heating device were connected to the silicone tubes to ensure regular blood supply and to prevent brain hypothermia. After performing the transplant surgery, the donor rat had pain and corneal reflexes, and the surgery opened up the possibility for the long-term survival of the patient.
Such scientific procedures have always drawn a lot of media frenzy and raised many ethical dilemmas. The first feeling people get when they hear "head transplant" or "brain transplant" is simply an ick. Funnily enough, they don't seem to respond in the same way when they hear about liver or kidney transplants. So far, head transplant surgeries have not been successful on live animal models, let alone on humans. While the ethical implications of such a procedure are immense, the technological limitations are such that it is too early to think about ethics. The largest technical limitation, like with any transplant, is still the immune response against the new "foreign" body. Even with increasing numbers and more frequent organ transplantations, particularly liver transplants, rejection still occurs very often, sometimes even a year after the surgery.