Studies demonstrate regeneration of mouse brain circuits with rat stem cells, providing new insights into neurological restoration and brain development across species. Credit: Issues.fr.com
Research teams have successfully regenerated mouse brain circuits using rat stem cells, presenting a new method for restoring brain function and studying cross-species brain development.
These findings open possibilities for treating neurological diseases and understanding brain evolution, while hinting at future clinical applications and the ethical challenges of using similar techniques for human organ transplantation.
Scientists regenerate mouse neural pathways with rat cells
Two independent research groups have successfully restored brain circuits in mice using neurons derived from rat stem cells. Recently published in the journal CellsThese studies provide important insights into brain tissue development and open new possibilities for rejuvenating brain functions lost to disease and aging.
“This research helps show the brain’s potential flexibility in using synthetic neural circuits to restore brain function,” says Kristin Baldwin, professor at Columbia University in New York and corresponding author of one of the two articles. Baldwin’s team restored the mouse’s olfactory neural circuits, the interconnected neurons in the brain responsible for the sense of smell, and their function using rat stem cells.
Mouse hippocampus with rat cells (red) and mouse and rat cell nuclei (blue). Credit: Mr. Khadeesh Imtiaz, Columbia University Irving Medical Center
Interspecies genetic engineering and its implications
“Being able to generate brain tissue from a species “Inside another can help us understand brain development and evolution in different species,” says Jun Wu, an associate professor at the University of Texas Southwestern Medical Center in Dallas and corresponding author of the other paper. Wu’s team developed a CRISPR-based platform that could efficiently identify the specific genes that drive the development of specific tissues. They tested the platform by silencing a gene required for forebrain development in mice and then restoring the tissue using rat stem cells.
Mice and rats are two distinct species that have evolved independently for approximately 20 to 30 million years. In previous experiments, scientists were able to replace the pancreas in mice using rat stem cells through a process called blastocyst complementation. To make this process work, researchers inject rat stem cells into mouse blastocysts – early-stage embryos – which lack the ability to develop a pancreas due to genetic mutations. The rat stem cells then grew to form the missing pancreas and completed its function.
Breakthroughs in brain tissue regeneration
But, to date, generation of brain tissue using stem cells of a different species by blastocyst complementation has not been reported. Now, using CRISPR, Wu’s team tested seven different genes and found that inactivation Hex1 could reliably generate mice lacking a forebrain. The team then injected rat stem cells into blastocysts of Hesx1 knockout mice, and rat cells filled the niche to form a forebrain in mice. Rats have larger brains than mice, but their forebrains grew at the same rate and size as those of mice. Additionally, rat neurons were able to transmit signals to neighboring mouse neurons and vice versa.
The researchers did not test whether the forebrain rat stem cells changed the mice’s behavior. “There are no effective behavioral tests to distinguish rats from mice,” says Wu. “But from our experience, it seems that these mice with rat forebrains do not behave in any unusual way. »
Advanced applications and future prospects
In the other study, Baldwin’s team used specific genes to kill or silence mouse olfactory sensory neurons used for the sense of smell and injected rat stem cells into the mouse embryos. The silencing model mimics what is seen in neurodevelopmental disorders, where some neurons cannot communicate well with the brain. The destruction model removed neurons entirely, thereby simulating degenerative diseases.
They found that blastocyst complementation restored mouse olfactory neural circuits differently depending on the model. When mouse neurons were present but silent, rat neurons helped form better organized brain regions compared to the destruction model. However, when the team tested these rat-mouse chimeras by training them to find a hidden cookie buried in a cage, the rat’s neurons were best at rescuing the killing model’s behaviors.
“This really surprising result allows us to examine what is different between these two disease models and try to identify mechanisms that might help restore function in either type of brain disease,” Baldwin explains. His team also tested blastocyst complementation in mouse disease models using cells from mice with normal olfactory systems. They showed that intraspecific complementation rescued cookie discovery in both models.
Exploring the frontiers of medical science
“Currently, people are receiving stem cell-derived neuron transplants to treat Parkinson’s disease and epilepsy in clinical trials. How well will this work? And will the different genetic backgrounds between the patient and the transplanted cells constitute a barrier? This study provides a system in which we can evaluate the possibilities of brain complementation of the same species on a much larger scale than a clinical trial,” says Baldwin.
Blastocyst complementation is still far from clinical application in humans, but both studies suggest that stem cells from different species can synchronize their development with the host’s brain.
Scientists have also experimented with growing human organs in other species, such as pigs, using blastocyst complementation. Last year, scientists generated embryonic kidneys from human stem cells in pigs, offering a potential solution for the many people waiting for transplants.
“Our aspiration is to enrich pig organs with a certain percentage of human cells, with the aim of improving outcomes for organ recipients. But at present, we still need to overcome many technical and ethical challenges before we can test this in clinical trials,” says Wu.
In addition to the medical implications of these studies, the teams also want to use this approach to study the brains of many wild rodents that were not accessible in the laboratory.
“There are more than 2,000 species of rodents living in the world. Many of them behave differently from the rodents we typically study in the lab. Interspecies complementation of neural blastocysts has the potential to open the door to studying how the brains of these species develop, evolve, and function,” Wu says.
To learn more about this research, see Mice modified with rat neurons show advanced sensory skills.
