Healthy Cells Successfully Transplanted to Repair Brain Without Anti-Rejection Drugs

Stem Cell Transplants May Help to Repair Brain, Study Shows

Researchers at Johns Hopkins reported that they have discovered a means of transplanting stem cells to repair the brain without having to use anti-rejection drugs in a study whose findings look to revolutionize how brain defects are treated.

Brain Stem Cell Research

Brain Stem Cell Research

To be able to transplant healthy cells to repair the brain of children without depending on life-long anti-rejection drugs is critical for those with rare genetic disorders of the brain. Every 1 in every 100,000 children born in America have such diseases according to estimates.

An example of these disorders is Pelizaeus-Merzbacher disease. This exhibits itself through developmental issues, such as the inability of infants to walk or sit at typical times for such milestones.

Findings by researchers in the new study, which was published in Brain, raises hope in the quest to develop effective treatments for these rare genetic disorders.

The scientists were able to develop a method which enabled them to successfully transplant stem cells without interference from the immune system. They did this without using anti-rejection medications that normally help to suppress an intrusive immune response.

The immune system detects transplanted cells as foreign bodies, which can cause it to attack them. This is where anti-rejection drugs come in to help prevent this effect. But another major challenge that arises from their use is that patients become more vulnerable to infections and other health issues.

This latest approach could potentially remove the use of these drugs at all when transplanting healthy cells for brain repair.

Checking the immune system

For this study, researchers were interested in finding ways to influence T cells of the immune system so that they stop attacking healthy cell transplants.

They aimed at altering a series of signals called “costimulatory signals” so that transplanted cells are not seen as invaders by the immune system. These signals play a role in the initiation of attacks by T cells.

The researchers injected glial cells, which form the protective myelin sheath around neurons, into the brains of mice. The cells, genetically-engineered to glow, were transplanted into three groups of mice. A group comprised of mice that were reared to be unable to produce glial cells. A second group featured normal mice, while the last group had mice engineered to not generate an immune response.

The scientists made use of two antibodies named CTLA4-Ig and anti-CD154. These antibodies are thought to inhibit T cells from receiving signals that usually cause them to attack foreign agents.

Treatment was halted after six days.

It was observed that mice which were given these antibodies were able to maintain transplanted cells in considerable amounts for more than 203 days.

“The fact that any glow remained showed us that cells had survived, even long after stopping the treatment,” said study lead author Dr. Shen Li. “We interpret this result as a success in selectively blocking the immune system’s T cells from killing the transplanted cells.”

However, the glial cells soon started dying off in mice that did not get the antibodies after transplantation. Their glow could no longer be detected using a specialized camera after 21 days.

Forming the myelin sheath

The researchers proceeded to investigate whether the transplanted glial cells performed their intended function of forming the myelin sheath. Using MRI imaging, they found that the cells were indeed functioning as intended in the treated mice.

The cells not only survived but also helped to form the myelin sheath that helps to shield neurons in the brain.

This suggests that the new approach may one day be helpful for the treatment of children with rare genetic disorders of the brain.

“Because these conditions are initiated by a mutation causing dysfunction in one type of cell, they present a good target for cell therapies, which involve transplanting healthy cells or cells engineered to not have a condition to take over for the diseased, damaged or missing cells,” said Piotr Walczak, a Johns Hopkins Medicine associate professor of radiology and radiological science.

These promising results are only preliminary, however, according to Walczak. The team looks forward to adding input from other research for a more thorough repair of the brain using this approach.

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