Stem cell transplant heals mouse brains with neurological deficits

Researchers at the University of Wisconsin-Madison have accomplished a notable feat in stem cell research that could lead to new models for drug screening and discovery--they have transformed human embryonic stem cells into nerve cells that helped mice regain the ability to learn and remember.

In what the UW scientists believe is the first study of its kind, a team led by senior author and professor of neuroscience and neurology Su-Chun Zhang successfully implanted the stem cells into mouse brains and observed that they healed neurological deficits.

"First, we are able to guide human pluripotent stem cells to enriched populations of neural progenitors that are involved in learning and memory," Zhang told FierceBiotechResearch. "Second, the human cells generate expected neuronal types with expected functions. And finally, this technology can also be used to produce the same types of neurons from patients' cells so that we can follow disease process and potentially use them for drug discovery."

Su-Chun Zhang

In the animal model, scientists used a special strain that do not refuse transplants from other species. The investigators deliberately killed the neurons in the medial septum part of the brain, which severed the connection between the medial septum and the hippocampus, causing memory and learning loss in mice. Scientists then generated septum-like cells and transplanted them directly to the hippocampus in the mice. The grafted cells made connections with the hippocampal neurons, which restored learning and memory deficits. 

After transplantation, the new stem cells formed two common, vital types of neurons, which communicate with the chemicals GABA or acetylcholine and are involved in a wide variety of human behavior, such as emotions, learning, memory, addiction and other psychiatric issues. The mice scored significantly better on learning and memory than they did before the transplant when the neurons in the medial septum were killed. The study appears in Nature Biotechnology.

Zhang said that it will take years until this kind of transplant could be replicated in humans. The obvious concern with embryonic stem cell treatments is their potential to form tumors in hosts. But his team is now using the technology to produce the same types of cells from patients with neurological conditions such as Down syndrome and Alzheimer's disease and to examine the pathological processes of these diseases. Zhang and his colleagues are also attempting to build drug-discovery platforms using this technology.

- here's the study abstract
- read the press release
- check out the Milwaukee Journal Sentinel blog post