Using Inflammatory Signaling to Lure Transplanted Stem Cells to Damaged Locations in the Body

Researchers here report on their efforts to improve stem cell therapies by steering the cells to migrate to areas of damage in the body. These cells travel through the body towards regions of inflammatory signaling. The researchers adapted one of these signal molecules to make it unlikely to significantly provoke cells into an inflammatory response, while still being attractive to stem cells. Using this molecule to steer stem cell migration to specific locations results in an improved efficacy of stem cell therapy in animal models, a good demonstration of the potential utility of this approach.

Nearly 15 years ago, researchers discovered that stem cells are drawn to inflammation, a biological "fire alarm" that signals damage has occurred. However, using inflammation as a therapeutic lure isn't feasible because an inflammatory environment can be harmful to the body. Thus, scientists have been on the hunt for tools to help stem cells migrate to desired places in the body. This tool would be helpful for disorders in which initial inflammatory signals fade over time - such as chronic spinal cord injury or stroke - and conditions where the role of inflammation is not clearly understood, such as heart disease.

In the study, the scientists modified CXCL12 - an inflammatory molecule which the team previously discovered could guide healing stem cells to sites in need of repair - to create a drug called SDV1a. The new drug works by enhancing stem cell binding and minimizing inflammatory signaling, and can be injected anywhere to lure stem cells to a specific location without causing inflammation.

To demonstrate that the new drug is able to improve the efficacy of a stem cell treatment, the researchers implanted SDV1a and human neural stem cells into the brains of mice with a neurodegenerative disease called Sandhoff disease. This experiment showed SDV1a helped the human neural stem cells migrate and perform healing functions, which included extending lifespan, delaying symptom onset, and preserving motor function for much longer than the mice that didn't receive the drug. Importantly, inflammation was not activated, and the stem cells were able to suppress any pre-existing inflammation.

The researchers have already begun testing SDV1a's ability to improve stem cell therapy in a mouse model of ALS, which is caused by progressive loss of motor neurons in the brain. Previous studies indicated that broadening the spread of neural stem cells helps more motor neurons survive, so the scientists are hopeful that strategic placement of SDV1a will expand the terrain covered by neuroprotective stem cells and help slow the onset and progressive of the disease.



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