By Marcia-Ruth Ndege ‘21

Human pluripotent stem cells can differentiate into nearly any cell in the human body. Recently, geneticist Abed AlFatah Mansour and other scientists from the Salk Institute for Biological Studies used them to build human brains in mice.

The differentiation of human pluripotent stem cells gave rise to small brain-like structures known as brain organoids about the size of a lentil. Researchers allowed the brain cells to grow a few millimeters in length to mimic the human brain in terms of number of cells, structure, and electrical activity. In addition, these organoids were genetically modified to express a fluorescent green protein visible through a glass implanted in the mice’s skull. Scientists then removed parts of over 200 mice’s brains to make space for the implantation of the organoids. 80% of the subsequent implants were successful. Using in vivo two-photon imaging, researchers were able to identify working neural networks and blood vessels in the grafts after only 14 days. This allowed for the transport of nutrients and oxygen, which in turn allowed for the cells’ survival for up to 233 days. The implanted cells sent neural impulses to both sides of the hosts’ brains, indicating full functionality; the presence of synapses between the human organoids and mice neurons also indicated that neural activity between the two was synchronized.

When mixing organs or tissues of two different species, researchers must always account for ethical questions. In the case of the Salk team, they had to consider if adding the human brain would affect the mice’s intelligence and consciousness. They discovered that the mixing of the brains did not result in more intelligent mice: the behavior of mice with the implants was the same as that of mice without the implants. Nonetheless, the researchers are hoping to develop this innovative approach as a means by which to further study brain development, diseases, and treatments.

References

1. A. Mansour, et. al., An in vivo model of functional and vascularized human brain organoids. Nature Biotechnology (2018). doi: 10.1038/nbt.4127.
2. Image retrieved from: https://www.pexels.com/photo/white-baby-mouse-159483/