17 June 2013

A new method of reprogramming fibroblasts into neurons

Astrocytes help differentiate neural stem cells into mature neurons

LifeSciencesToday based on materials from Penn State University:
Alzheimer's, Schizophrenia, and Autism Now Can Be Studied with Mature Brain Cells Reprogrammed from Skin CellsDiseases that are difficult to study, such as Alzheimer's disease, schizophrenia, autism, can now be studied more safely and effectively – using an innovative method of obtaining mature brain neurons derived from reprogrammed skin cells.

The head of the research group, Gong Chen, professor of biology at Penn State University, believes that the most exciting thing about his work is that it gives hope for direct modeling of diseases, allowing you to create mature human neurons in a Petri dish, very similar to the natural neurons of the human brain. In his opinion, the results of this study, published in the journal Stem Cell Research (Tang et al., Astroglial cells regulate the developmental timeline of human neurons differentiated from induced pluripotent stem cells), can help in the development of personalized treatments based on the genetic and cellular information of a particular patient.

"Of course, we don't want to take cells from someone's brain to conduct experiments on them, so recreating a patient's neurons in a Petri dish is the best alternative for scientific research and drug screening," says Professor Chen.

Scientists already know how to reprogram patients' skin cells into non-specialized, or undifferentiated, so-called induced pluripotent stem cells (iPSCs, iPSCs). Pluripotent stem cells are a kind of blank slate. During development, they differentiate into various specialized cell types, such as muscle, brain, or blood cells. Thus, after obtaining iPSCs from skin cells, scientists can reprogram them into neurons that can be studied in a Petri dish without risk to the patient.

Professor Chen and his colleagues have found a more effective way to differentiate induced pluripotent stem cells into mature human neurons. In their natural environment, neurons are always in close proximity to the stellate cells of glia – astrocytes, which are abundantly present in the brain and help the normal functioning of neurons.

"Since brain neurons are located next to astrocytes, we hypothesized that this direct physical contact may be an integral part of the growth and healthy state of neurons," Chen continues.

To test this hypothesis, he and his colleagues began by cultivating neural stem cells derived from iPSCs that have the potential to differentiate into neurons. Neural stem cells were cultured on a layer of astrocytes one cell thick, and thus these two types of cells were physically in contact with each other.

"We found that neural stem cells cultured on astrocytes differentiated much more efficiently into mature neurons," Chen says. "It was as if astrocytes were encouraging stem cells, telling them what to do and helping them follow their destiny–to become neurons."

When cultured with astrocytes, human neural stem cells (shown in red),
originally reprogrammed from adult skin cells,
effectively differentiate into mature neurons (shown in green).
(Photo: Chen lab, Penn State University)

The experiment conducted by scientists confirmed the advantage of neurons grown next to astrocytes: they had significantly more synaptic events – interneuronal signals. In another experiment–on neural stem cells that developed next to astrocytes for just one week– the researchers demonstrated that newly differentiated neurons generate an action potential– a fast electrical wave of excitation characteristic of all neurons in the brain. In the final test, they mixed human neural stem cells with mouse neurons.

"We found that just a week later, human and mouse neurons began to actively "roll call". Such a roll call occurs when a neuron contacts neighboring nerve cells and releases chemicals – neurotransmitters – modulating the activity of neighbors," Chen comments on the experiment.

"Previously, scientists could obtain brain cells from patients with diseases such as Alzheimer's disease, schizophrenia and autism only after the death of patients," the professor continues. "It is now possible to take skin cells from living patients – a safe and minimally invasive procedure – and reprogram them into brain cells that mimic the functions of the patient's own cells. In addition, using this method, scientists can find out how much a particular drug will affect the brain cells of a particular patient. Patients will not need to take and, in fact, test medications themselves, which will eliminate the risk of serious side effects.

"The patient will become a guinea pig to develop a drug for his treatment, but there will be no need to experiment directly on him," the scientist concludes.

Portal "Eternal youth" http://vechnayamolodost.ru17.06.2013

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