Prof. Joseph Yanai of the Hebrew University of Jerusalem.Israeli scientists have succeeded in reversing brain birth defects in animal models, using embryonic stem cells to replace defective brain cells.

The findings could lead in the long term to a significant breakthrough in the treatment of neural and behavioral birth defects, such as learning disabilities, which are particularly difficult to treat. Unlike neural disorders such as Parkinson’s or Alzheimer’s, the prenatal teratogen – the substances that cause the abnormalities – act diffusely in the fetal brain, resulting in multiple defects.

A team of researchers from the Hebrew University of Jerusalem-Hadassah Medical led by Prof. Joseph Yanai, were able to overcome this obstacle in laboratory tests with mice, by using mouse embryonic neural stem cells. These cells migrate in the brain, search for the deficiency causing the defect, and then differentiate into becoming the cells needed to repair the damage.

Stem cells may develop into any type of cell in the body, however at a certain point they commit to a general function, such as neural stem cells, destined to play a role in the brain or nervous system. At more advanced developmental stages, the neural stem cells take on an even more specific role as neural or glial (supporting) cells within the brain or nervous system.

Reversing learning deficits

In the animal model, the researchers, including Prof. Tamir Ben-Hur, head of the Department of Neurology at the Hebrew University-Hadassah Medical School and Prof. Ted Slotkin at Duke University in North Carolina, where Yanai is an adjunct professor, were able to reverse learning deficits in the offspring of pregnant mice who were exposed to heroin and the pesticide organophosphate.

This was done by direct neural stem cell transplantation into the brains of the offspring. The recovery was almost 100 percent, as proved in behavioral tests in which the treated animals improved to normal behavior and learning scores after the transplantation. On the molecular level, brain chemistry of the treated animals was also restored to normal.

Through the work, which was supported by the US National Institutes of Health, the US-Israel Binational Science Foundation and the Israel anti-drug authorities, the researchers discovered that the stem cells worked even in cases where most of the cells died out in the host brain.

The scientists found that before they die the neural stem cells succeed in inducing the host brain to produce large numbers of stem cells which repair the damage. These findings, which answered a major question in the stem cell research community, were published earlier this year in the leading journal, Molecular Psychiatry.

Looking for a clinically-feasible therapy

The work of Yanai and his associates was also presented at the second International Stem Cell Meeting in Tel Aviv last spring and is expected to be presented and published next year at the seventh annual meeting of the International Society for Stem Cell Research in Barcelona, Spain.

The scientists are now developing procedures to administer the neural stem cells in the least invasive way possible – probably via blood vessels. This will make the therapy practical and clinically feasible.

Today, transplanted stem cells are normally derived from individuals genetically different from the patient, and treatments can lead to immunological rejection. With this in mind, the researchers also plan to work on developing methods to take cells from the patient’s own body, turn them into stem cells, and then transplant them back into the patient’s blood via the blood stream.

Aside from decreasing the chances of immunological rejection, the approach will also eliminate the controversial ethical issues involved in the use of stem cells from human embryos.