Scientists have successfully produced a neonatal 'chimeric' monkey, marking a significant advancement in genetic research. This result opens new possibilities for studying human diseases and developing treatments using chimeric monkeys, which share a greater biological resemblance to humans than chimeric rats and mice. However, the study raises ethical concerns and emphasizes the need for further optimizations of the approach.
Researchers have long sought to create animal chimeras using embryonic stem cells, which can develop into various tissues. These stem cells can be genetically modified before being incorporated into a recipient embryo, allowing scientists to study the effects of specific mutations on physiology and health.
While pluripotency has been extensively demonstrated in rodents, achieving it in other species, including non-human primates, has been challenging due to difficulties in aligning the developmental state of donor cells with that of host embryos. In previous attempts with chimeric monkeys, only a minimal percentage (0.1-4.5%) of cells in organs such as the brain, kidney, and lungs originated from donor stem cells, rendering them unsuitable models for human diseases. This study adopted a different, more robust approach to create recipient embryos with a greater contribution from donor stem cells. Researchers collected eggs from female cynomolgus monkeys (Macaca fascicularis) and fertilized them to create recipient embryos. Simultaneously, they extracted embryonic stem cells from one-week-old cynomolgus embryos, genetically modifying the cells to exhibit a green fluorescent signal. By optimizing nutrients and growth-promoting proteins in the laboratory culture, the team refined the conditions for the growth of these stem cells. Subsequently, up to 20 fluorescent embryonic stem cells were injected into each recipient embryo, resulting in 74 chimeric embryos displaying a strong fluorescent signal. However, the success rate was modest, with only one live chimeric monkey born out of 40 surrogate monkeys implanted with chimeric embryos. The euthanasia of the chimeric monkey after ten days due to hypothermia and respiratory difficulties emphasized the need for further refinements in the approach.
The research also highlights challenges associated with current genetic modification techniques in non-human primates, emphasizing limitations in terms of efficiency. It suggests an alternative approach based on the use of homologous embryonic stem cells, which has the potential to overcome these limitations. Additionally, the paper outlines the process of optimizing culture conditions for naive monkey embryonic stem cells and the protocol for in vitro culture of chimeric embryos. The results demonstrate that culturing in a specific medium, referred to as 4CL, produced a better pluripotent state for monkey embryonic stem cells, facilitating the survival of donor cells in chimeric embryos.
Despite challenges, the study has been praised for its remarkable results. Scientists speculate that this method could be employed to grow human organs in pig or non-human primate tissues. By deleting specific genes, such as those for the kidney, in these animals and introducing human cells, it might lead to the production of human organs. However, ethical concerns arise, especially if human embryonic stem cells contribute to critical systems like the nervous system, brain, or reproductive cells. While the study marks a significant breakthrough in creating chimeric monkeys with a higher contribution of donor stem cells, it prompts a thoughtful reflection on ethical implications and the need for further refinements. Balancing scientific progress with ethical responsibilities will be crucial as researchers explore potential applications of this pioneering research in the future.