Neural Stem Cells Steered By Electric Fields in Rat Brain

Scientists at the University of California, Davis School of Medicine’s Institute for Regenerative Cures report that electric fields can be used to guide neural stem cells transplanted into the brain toward a specific location. Their study (“Electrical Guidance of Human Stem Cells in the Rat Brain”), which appears in Stem Cell Reports, opens possibilities for effectively guiding stem cells to repair brain damage.

“…we report a strategy that mobilizes and guides migration of stem cells in the brain in vivo. We developed a safe stimulation paradigm to deliver directional currents in the brain,” write the investigators. “Tracking cells expressing GFP [green fluorescent protein] demonstrated electrical mobilization and guidance of migration of human neural stem cells, even against co-existing intrinsic cues in the rostral migration stream.”

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Min Zhao, M.D., Ph.D., carries out research on how electric fields can guide wound healing. Damaged tissues generate weak electric fields, and Zhao’s research has shown how these electric fields can attract cells into wounds to heal them.

“One unmet need in regenerative medicine is how to effectively and safely mobilize and guide stem cells to migrate to lesion sites for repair,” Dr. Zhao said. “Inefficient migration of those cells to lesions is a significant roadblock to developing effective clinical applications.”

Natural neural stem cells are found deep in the brain, in the subventricular zone and hippocampus. To repair damage to the cortex, they have to migrate some distance, especially in the large human brain. Transplanted stem cells might also have to migrate some way to find an area of damage.

Dr. Zhao, and his colleague, Junfeng Feng, M.D., a neurosurgeon at Ren Ji Hospital, Shanghai Jiao Tong University, and Shanghai Institute of Head Trauma, developed a model of stem cell transplants in rats. They placed human neural stem cells in the rostral migration stream, which is a pathway in the rat brain that carries cells toward the olfactory bulb. Cells move along this pathway, partly carried by the flow of cerebrospinal fluid and partly guided by chemical signals.

By applying an electric field within the rat’s brain, the scientists found that they could get the transplanted stem cells to swim upstream against the fluid flow and natural cues and head for other locations within the brain.

The transplanted stem cells were still in their new locations weeks or months after treatment.

“Electrical mobilization and guidance of stem cells in the brain therefore provides a potential approach to facilitate stem cell therapies for brain diseases, stroke, and injuries,” noted Dr. Zhao.

What is preclinical testing?

In the process of preclinical testing of a compound or biological agent into a drug, the compound involved must go through the testing phase. First, we need to identify potential targets that can treat the disease. Then, a variety of compounds or preparations are screened out. Any compound that has shown potential as a drug for the treatment of this disease needs to be tested for toxicity before clinical testing to reduce the possibility of injury. preclinical testing What is the basis of preclinical testing? According to US Food and Drug Administration (FDA) regulations, a series of tests are required before a new drug is approved for use. In the first stage, basic research determines a hypothetical target for the treatment of a certain disease, and then screens small molecules or biological compounds to discover any substance with the potential to treat the disease. Then, a preclinical research phase followed, before which, as described above, the potential toxicity of the compou

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Inventory of the three major in vitro pharmacokinetic research methods

The metabolic properties of a compound are an essential factor in whether or not it can be used as a drug in the clinical setting, so pharmacokinetic studies of newly synthesized compounds are required in drug development. In vitro incubation with liver microsomes, recombinant CYP450 enzyme lines, and in vitro incubation with hepatocytes are some of the more common in vitro drug metabolism methods. 1. In vitro incubation method with liver microsomes The metabolic stability and metabolic phenotypes of candidate compounds in different species of liver microsomes are good predictors of the metabolic properties of compounds in vivo. They are practical tools for evaluating candidate compounds in the pre-development phase of drug development. Liver microsomes include rat liver microsomes, human liver microsomes, canine liver microsomes, monkey liver microsomes, and mouse liver microsomes. In in vitro incubation of the liver, microsomes are the "gold standard" for in vitro d

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Novel Parkinson’s Therapies Possible with New Mouse Model

Parkinson's disease (PD) is a neurodegenerative disorder that is marked by the accumulation of the protein, α-synuclein (αS), into clumps known as Lewy bodies, which diminish neural health. Now, researchers from Brigham and Women's Hospital (BWH) report the development of a mouse model to induce PD-like αS aggregation, leading to resting tremor and abnormal movement control. The mouse responds to L-DOPA, similarly to patients with PD. The team's study (“Abrogating Native α-Synuclein Tetramers in Mice Causes a L-DOPA-Responsive Motor Syndrome Closely Resembling Parkinson’s Disease”) on the use of this transgenic mouse model appears in Neuron . “α-Synuclein (αS) regulates vesicle exocytosis but forms insoluble deposits in PD. Developing disease-modifying therapies requires animal models that reproduce cardinal features of PD. We recently described a previously unrecognized physiological form of αS, α-helical tetramers, and showed that familial PD-causing missense mutati

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