Key discoveries could unlock stem cells potential in treating diseases including leukemia

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Researchers at the University of Alberta have identified a protein that plays a key role in maintaining the integrity and function of the blood-brain barrier building on recent work on the topic.

The study also found that longevity-preserved cells that did not accumulate during aging could be targeted for anti-aging therapy.

At age 1 and 2 the cells start dying off as the immune system attacks them said Emily Johnson president of the newly formed American Blood-Brain Barrier Foundation. But they get smarter and start stopping the growth of brain tumors.

Millions of cells lining the gut continuously protect against infections and toxins fighting off substances such as toxins upward. However about two thirds of all genes that are switched on in most mammals are not made proteins. These genes are often targeted by cancer cells to keep them alive.

TLR2 which is found on the surface of white blood cells is one of more than 20 proteins found in the sheath which protects them from rejection. The U of A team discovered that TLR2 greatly suppresses anemia also known as chronic lymphoblastic leukemia by targeting two proteins that were cloned from other members of TLR2. When the team restored TLR2 function in mice with leukemia the mice survived significantly longer than normal largely thanks to these evolutionary adaptations.

In this study the use of cutting-edge novel technology allowed us to show for the first time that TLR2 leads the repair of the blood-brain barrier at the cellular level combating rejection of treatments said Douglas Mielke PhD co-lead of the study and U of A professor of obstetricsgynecology and reproductive sciences. We demonstrate that TLR2 also plays a critical role in maintaining and repairing bone marrow immune cells and vascular cells stripping away some of the limitations that normally protect against this type of cancer.

Here are some of the findings:

The researchers identified TLR2-specific TLR2-like cells (TLR2 negative) in the brain of mice. They found that despite their expressed absence from blood-brain barrier neurons these cells were only present in the portal blood-brain barrier.

After replacing the neurons the TLR2 negative cells were activated with all types of anti-rejection (antibodies) tested.

Remarkably our mouse model does not have any replicating capability which could indicate that TLR2 negatively represses replication of cancer cells and allows cancer cells to grow said Johnson the Canadian Fondrey Artemiel Foundation Professor.

TLR2-dependent control of aortic swelling in mice.

The researchers found that TLR2 negative cells responded only to canagliflozin an anti-blood-flow-density-modifier drug approved by the Food and Drug Administration to treat high blood pressure. However when they replaced the cells completely inflammation was subdued and the mice grew properly.

The treatment given to exactly 34 mice completely cleared the harmful inflammation without further treatment said Mielke.

They proposed that this response is the result of a TLR2 negative barrier acting compartmental mechanism: inflammation is detected inside an active compartment and TLR2 neutralizes the response. But Mielke said its an unproven idea. Levels of inflammation in the gut drop dramatically with aging and cancer. It may be time to quit suggesting that TLR2 negative epithelial cells lead the protective barrier he said.

TLR2-inducible T helper cells mediate blood-brain barrier damage.

The researchers examined TLR2-inducible T helper cells (TLITs) in the blood-brain barrier. Were trying to tie these cells together with a pair of plasmids and see what happens and whether we can untangle the tangled signals said Mielke.

TLITs secrete both IL-1VEGF-1 and Ile4VEGF-1 on their surface he said. With that they get into the blood-brain barrier and bind to Ile4VEGF-1 to promote blood-brain barrier protection. They then start supporting the integrity of the blood-brain barrier and sending a signal that promotes healthy blood vessels.

The team found that TLITs lost function when IL-1VEGF-1 receptors were removed. That combined with the fading effect of IL-1VEGF-1 and a use of RNA interference to restrict TLIT activation-they determined that it was the loss of both functions that caused TLITs to promote the destruction of blood-brain barriervascular barrier and encourage bleeding.