Conditions that are difficult to study — such as schizophrenia, autism and Alzheimer’s — can now be analyzed safely and effectively with an innovative method designed to retrieve mature brain cells from reprogrammed skin cells, according to research published in the journal Stem Cell Research.
“Obviously, we don’t want to remove someone’s brain cells to experiment on, so re-creating the patient’s brain cells in a petri dish is the next best thing for research purposes and drug screening,” said research leader Gong Chen, Ph.D., professor of biology at Penn State University.
“The most exciting part of this research is that it offers the promise of direct disease modeling, allowing for the creation, in a petri dish, of mature human neurons that behave a lot like neurons that grow naturally in the human brain.”
Chen believes that the method could lead to customized treatments for individual patients based on their own genetic and cellular information. He said that, in previous research, scientists had found a way to reprogram skin cells from patients to become unspecialized or undifferentiated pluripotent stem cells (iPSCs).
“A pluripotent stem cell is a kind of blank slate,” Chen said. “During development, such stem cells differentiate into many diverse, specialized cell types, such as a muscle cell, a brain cell, or a blood cell. So, after generating iPSCs from skin cells, researchers then can culture them to become brain cells, or neurons, which can be studied safely in a Petri dish.”
Now, in the new study, researchers have found a way to differentiate iPSCs into mature human neurons much more effectively, generating cells that behave like neurons in the brain. Chen explained that, in their natural environment, neurons are always found in close proximity to star-shaped cells called astrocytes, which are abundant in the brain and help neurons function correctly.
“Because neurons are adjacent to astrocytes in the brain, we predicted that this direct physical contact might be an integral part of neuronal growth and health,” said Chen.
To test this hypothesis, the team began by culturing iPSC-derived neural stem cells, which are stem cells that have the potential to become neurons. These cells were cultured on top of a one-cell-thick layer of astrocytes so that the two cell types were physically touching each other.
“We found that these neural stem cells cultured on astrocytes differentiated into mature neurons much more effectively,” Chen said, contrasting them with other neural stem cells that were cultured alone in a petri dish. “It was almost as if the astrocytes were cheering the stem cells on, telling them what to do, and helping them fulfill their destiny to become neurons.”
Next, the researchers used an electrophysiology recording technique to show that cells grown on astrocytes had many more synaptic events—signals sent out from one nerve cell to the others. Then, after just one week, the newly differentiated neurons began firing action potentials — the rapid electrical excitation signal that occurs in all neurons in the brain.
Finally, the researchers added human neural stem cells to a mixture with mouse neurons. “We found that, after just one week, there was a lot of ‘cross-talk’ between the mouse neurons and the human neurons,” Chen said.
He explained that “cross-talk” occurs when one neuron contacts its neighbors and releases a neurotransmitter to modulate its neighbor’s activity.
“Previous researchers could only obtain brain cells from deceased patients who had suffered from diseases such as Alzheimer’s, schizophrenia, and autism,” Chen said. “Now, researchers can take skin cells from living patients — a safe and minimally invasive procedure — and convert them into brain cells that mimic the activity of the patient’s own brain cells.”
With this method, clinicians would know how a certain drug would affect a particular patient’s own brain cells, without even trying the drug — eliminating the risk of serious side effects.
“The patient can be his or her own guinea pig for the design of his or her own treatment, without having to be experimented on directly,” he said.
Source: Stem Cell Research