Reacción a "Reactions: scientists regenerate neural pathways in mice with rat cells"

The publications by Huang et al. and Throesch et al. deal with the production and investigation of chimeras between mice and rats. Chimeras are organisms that consist of cells that originate from two different fertilization processes (embryos). A distinction must be made between intra- and interspecies chimeras. In intraspecies chimeras, the chimeric cells both belong to the same species. For example, mouse-mouse chimeras are used in the studies published here. In these new studies, however, interspecies chimeras between mouse and rat are also produced. In this case, the cells that form an organism originate from two different species. Interspecies chimeras in particular are of great interest from a developmental and evolutionary biology perspective. However, interspecies chimeras can also provide very valuable insights regarding the production of transplantable organs for human medicine. This is a high-priority research goal in view of the decades-long shortage of donor organs for transplantation in patients.

Chimeras must be clearly distinguished from hybrids. In contrast to chimeras, hybrids develop from just one fertilized egg cell. In hybrids, however, the male sperm and the female egg come from two different (but closely related) species. For example, the sperm of a donkey can successfully fertilize the egg of a horse. The resulting embryo develops into a mule. In a hybrid, all the individual cells of the organism itself are already a ‘mixture’ of the two parent species. In an interspecies chimera, on the other hand, each individual cell is clearly assigned to one species.

In the two current studies, the chimeras are generated experimentally at the so-called blastocyst stage. Around ten ‘all-rounder’ stem cells are injected into an embryo that is a few days old and around a tenth of a millimeter in size, which at this stage is a small fluid-filled bubble of cells. The injected stem cells integrate into the recipient embryo and co-develop with it more or less efficiently until birth. The integration of the injected stem cells is much more efficient if the recipient embryo is unable to form individual tissues or organs itself due to a specific genetic modification. These free anatomical niches in the developing embryo are then taken up and filled particularly efficiently by the injected chimeric cells. This process is known as blastocyst complementation.

Huang et al. can be credited with making the blastocyst complementation process much faster by combining the genetic methods for opening a niche into which the chimeric cells can efficiently implant with the methods of previous blastocyst complementation in one step. This new combined technology will greatly accelerate chimera research - especially in larger mammals with a longer generation time. Given that some of the authors of this study work at a Chinese primate center, it can be assumed that this technology will now also be used in non-human primates.”
“Throesch et al. were able to show for the first time that chimeric cells could compensate for the loss of embryonic nerve cells not only structurally but also functionally. Thus, chimeric mice were able to find hidden food in a more targeted manner using a sense of smell restored by rat cells. A mouse’s complex behavior was thus triggered by a rat’s sense of smell. The mouse smelled the food with a rat’s nose, so to speak.

Chimera research helps to generate knowledge in order to make cell and tissue replacement therapies available to patients more quickly. However, the chimera creation approach presented here is not an approach that can be directly transferred to humans as a therapy. The work presented here is very valuable for a better understanding of the embryonic development of brains, their evolutionary adaptations and how they function.

Accompanying bioethical research is necessary at the latest when human embryos are to be used as recipients in chimera research. Personally, I would strictly reject the use of human embryos in interspecies chimera research, even if this were permitted in Germany. But even if human stem cells are transplanted into animal embryos, which may make sense from a biomedical point of view, a biomedical-bioethical discourse should take place.

Modern chimera research is still in its infancy. Important fundamental findings can currently be obtained from practically every chimera study, which in their entirety strongly promote the concept of growing replacement organs from human cells for organ transplants, for example in pigs. In my opinion, the two studies that have now been published do not yet provide a translational approach for new therapeutic approaches. However, they contribute significantly to the scientific knowledge on which new therapies can be built in the long term.