Innovative Brain Stem Cell Transplant Method Developed

Challenges in Neurological Disease Treatment

Several neurological diseases are treated through brain stem cell transplants. A significant challenge associated with this therapy is the rejection of transplanted cells by the body’s immune system. Researchers at Johns Hopkins Medicine have created a groundbreaking approach to counteract this rejection, eliminating the need for long-term anti-rejection medications.

Impact of Neurological Disorders

Neurological conditions, including Pelizaeus-Merzbacher disease, affect approximately one in every 100,000 children in the United States. Brain stem cell transplants are commonly employed to replace damaged or absent cells with healthy alternatives. Traditionally, these transplants require patients to take anti-rejection drugs to prevent their immune systems from attacking the foreign cells, which can lead to various side effects and increased susceptibility to infections.

Research Findings on Co-Stimulatory Molecules

The recent findings from Johns Hopkins, published in the journal Brain, highlight a method to minimize side effects associated with anti-rejection drugs. Researchers focused on “co-stimulatory molecules” and sought a way to modify T-cells, the primary defenders against foreign substances in the body. They concentrated on co-stimulatory signals that protect the immune system from attacking its own cells. By blocking these signals with antibodies such as CTLA4-Ig and MR-1, the team trained the immune system to identify transplanted cells as “self.”

Biomarkers for Transplant Acceptance

The study also identified new biomarkers related to transplant acceptance. Researchers discovered specific miRNAs, including miR-146, miR-223, and let-7a/7c, that can predict whether the immune system has accepted the transplanted cells. These miRNAs are small RNA molecules that regulate T-cell activity.

Experimental Approach with Mice

The research was conducted using mice, including genetically engineered mice designed to block co-stimulatory signals, immunodeficient mice, and normal mice. The scientists injected the brains of these mice with glial cells that produce the myelin sheath for neurons. These glial cells were engineered to glow, allowing for detection using a specialized camera.

Normal mice with active co-stimulatory signals experienced loss of the transplanted cells, with no glow detected by day 21. However, in mice where the co-stimulatory signals were blocked, the transplanted cells survived and functioned for over 200 days. The functional capacity of these cells was evaluated through MRI, with comparisons made between the brains of mice with surviving transplanted cells and those without, demonstrating normal cell function.

MiRNA Levels and Graft Rejection

Among the miRNAs studied, increased levels of miR-146 were correlated with graft rejection in brain stem cell transplants. Conversely, levels of miR-146 and miR-223 decreased in mice with co-stimulatory blockade.

Future Implications of the Study

This study presents new possibilities for brain stem cell transplants and offers hope for future successful treatments of various neurological disorders. However, researchers emphasize that these findings are preliminary and necessitate further investigation.

References

Li, S., Oh, B., Chu, C., Arnold, A., Jablonska, A., Furtmüller, G., Qin, H., Boltze, J., Magnus, T., Ludewig, P., Janowski, M., Brandacher, G., and Walczak, P. (2019). Induction of immunological tolerance to myelinogenic glial-restricted progenitor allografts. EurekAlert!. (2019). In mice: Transplanted brain stem cells survive without anti-rejection drugs. Available at: https://www.eurekalert.org/pub_releases/2019-09/jhm-imt091319.php [Accessed 23 Sep. 2019].

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