Lab-Grown Human Brain Tissue Transplanted Into Mouse Brains
Researchers have successfully transplanted lab-grown human brain tissue into mouse brains, where the tissue survived, developed and produced a variety of human brain cells, according to a study published in Nature.
The findings suggest a potential new model for studying human brain development and neurological disorders by allowing scientists to observe human brain tissue in a living organism.
The transplanted tissues, known as brain organoids, were also able to organise into neural circuits and develop complex structures resembling cortical tissue.
Researchers at Stanford University in the US said the experiments were carried out in accordance with ethical guidelines. They said the approach could provide a useful tool for investigating brain development, disease mechanisms and potential treatments.
Studying human brain development has long been challenging because access to living human brain tissue is extremely limited. Stem-cell-based models, including brain organoids, have helped scientists overcome some of these limitations.
According to the researchers, transplanting brain organoids into rodents provides an opportunity to examine how human neurons develop and function within a living brain and could help researchers study neurological diseases and possible therapies.
However, earlier transplantation experiments faced limitations because of the restricted space available in the mouse brain and competition between human and mouse neurons. To address this problem, the researchers developed genetically modified mice with depleted areas of the cortex, creating space for human brain organoids to integrate.
The transplanted organoids grew successfully and occupied much of the available space. They developed into multiple types of human brain cells and formed neural circuits and complex structures resembling the cerebral cortex.
The researchers also found that the integrated human cortical tissue may influence behaviour. Comparisons between mice with depleted cortex regions, with and without transplanted organoids, showed differences in tasks involving motor skills and memory.
The researchers said the new model could allow scientists to study aspects of human brain development in greater detail than previously possible.
The authors "establish a transplantation platform using a genetic strategy to effectively deplete glutamatergic neurons from mouse neocortex and hippocampus (apallial) and neonatally engraft the cortical cavity with human stem-cell-derived cortical organoids (hCO) to generate xenocortical mice."
Adeel Razi, professor of computational neuroscience at Monash University in Australia, described the research as "very elegant and ambitious" and said it could be "particularly useful for studying developmental injury and neurodevelopmental diseases, like ADHD and autism."
"The proposed system creates an unusual experimental platform for studying biological intelligence. It will help disentangle what properties of human cortical organisation are intrinsic to the human brain from what is imposed by the developmental phase and surrounding mouse host brain circuitry," Razi, who was not involved in the study, said.
However, Razi cautioned against interpreting the findings as evidence that the transplanted human tissue functions like a mature human brain.
"The functional integration of human-derived brain cells is not a proxy for its functional equivalence. The grafted human brain tissue lacks features of mature human brain tissue. And the recorded behaviour emerges from the interactions of the human cortex and the remaining mouse subcortex," he said.
"Hence, the limitation of the technique is that it is difficult to know whether the grafted human brain cells are necessary or sufficient for a particular observed behaviour," Razi said.ALSO READ: Enlarged Prostate Treatment: Delhi Hospital Introduces Steam Therapy
