A team of University of Florida Health researchers has successfully transplanted human stem cells that developed into fully functional neurons in a mouse model, a promising step toward finding new treatments for epilepsy and other neurological disorders.
The findings are particularly encouraging for two reasons, said Steven N. Roper, M.D., a neurosurgeon and professor in the UF College of Medicine department of neurosurgery. Not only did the human stem cells survive after being transplanted, but they also developed into neurons that behave normally within the brain. The findings were published March 12 in the journal PLOS One.
For people with epilepsy, stem cell transplantation offers the prospect of someday preventing seizures, which are marked by uncontrolled muscle contractions and sometimes unconsciousness. Medications aren’t always effective and only control the symptoms of epilepsy, which affects between 1.3 million and 2.8 million people in the United States, according to the Epilepsy Foundation of America. In some severe cases, seizures are controlled by surgically removing part of the brain.
During the study, implanted human neural stem cells survived for eight weeks in a mouse model and developed into three types of “connector” neurons called interneurons. It’s those neurons that could someday be used to treat various neurological diseases. With epilepsy, the implanted cells could be used to produce inhibitory neurons to calm the firestorm of overexcited brain cells that cause seizures. In the study, 15 percent of the stem cells became excitatory neurons. These cells could also have potential applications in other types of human conditions such as stroke or traumatic brain injury.
After implanting the human stem cells, the research group made a groundbreaking discovery: The transplanted neurons fully integrated into the brain, and researchers made detailed recordings of their electrical activity. That is especially significant because it shows the transplanted cells will communicate with existing neurons in the host, Roper said. Researchers also were able to characterize the different kinds of neurons that evolved from the stem cells, he said.
“This shows that human stem cells are quite capable of providing the different cell types that we need to treat various diseases. This makes us very optimistic that these cells can ultimately be used for a number of different human diseases that require better control of brain function,” Roper said.
In addition to epilepsy, stem cell implantation could also be a potential treatment for Alzheimer’s and Parkinson’s diseases, strokes and perhaps even depression, Roper said.
“If you can harness that potential, you can start to control any particular area of the brain as long as you know what’s needed,” Roper said.
Neural stem cells offer another advantage as research into neurological disorders moves forward: Unlimited quantities of them can be grown in a laboratory, said Brent Reynolds, Ph.D., a professor in the department of neurosurgery who collaborated on the study. While other researchers have successfully implanted human neural stem cells, knowing they can ultimately bond with the brain and become active is crucial. That’s one of the novel things about the research, Reynolds said.
Before that happens, researchers have some practical issues to address. The survival rate of transplanted cells was 1 percent, a figure Roper said is “fairly low” but can be improved. He also wants to test the cells in animal models with a normal immune system. To prevent rejection of the transplanted cells, mouse models without an immune system were used in the recent study.
“We also need to learn how to control the fate of the neural stem cells that are transplanted so that a specific type of neuron can be used to treat a specific disease,” Roper said.
“It’s going to be a much better way of treating diseases than we currently have available,” he said. “It’s not going to be tomorrow, but the fact that we’re using human stem cells means we’re already working on that next critical step.”