Wisconsin Scientists Use Stereo Investigator to Quantify Neurons Formed From Stem Cells

Researchers at the Waisman Center (University of Wisconsin-Madison) just took a big step in their quest to develop regenerative medicines for treating Parkinson’s, Alzheimer’s, and other neurodegenerative diseases. They used human embryonic stem cells to restore memory and learning in disabled mice.

The study, published last month in Nature Biotechnology, “is the first to show that human stem cells can successfully implant themselves in the brain and then heal neurological deficits,” senior author Su-Chun Zhang told the University of Wisconsin-Madison news department.

Using chemicals known to promote neuron development, Dr. Zhang‘s team cultured the stem cells in vitro. Once the cells reached a state of partial differentiation, meaning they were on their way to developing into neurons, they were injected into the hippocampi of a group of mice. The mice, members of a strain that does not reject transplants from other species, had received injury to their medial septum brain region. According to the paper, this brain region is involved in learning and memory, and is connected to the hippocampus by GABA and cholinergic neurons.

The researchers used a variety of methods, including stereology with an MBF system available at the The Waisman Center’s Core Imaging facility (Stereo Investigator software coupled with a Zeiss fluorescence microscope), to analyze the postmortem brains. They determined that the stem cells had successfully developed into basal forebrain cholinergic neurons (BFCNs) and GABAergic neurons that became integrated into the circuitry of the mouse brains.

Behavioral tests such as the Morris water maze, showed that the mice performed better in tasks related to learning and memory after cell transplant, leading the researchers to conclude that the new cells had corrected deficits in these areas.

“Our findings support the prospect of using human stem cell-derived MGE-like progenitors in developing therapies for neurological disorders of learning and memory,” the authors say in their paper.

Liu, Y., Weick, J., Liu, H., Krencik, R., Zhang, X., Ma, L., Zhou, G., Ayala, M., & Zhang, S. (2013). Medial ganglionic eminence–like cells derived from human embryonic stem cells correct learning and memory deficits Nature Biotechnology DOI: 10.1038/nbt.2565