Bait for stem cells
Researchers from the Burnham Institute for Medical Research (Sanford Burnham Prebys Medical Discovery Institute) have created a drug that attracts stem cells into damaged tissues and increases the effectiveness of treatment. This is an important achievement in the field of regenerative medicine, it will help improve existing methods of stem cell treatment of neurological disorders (spinal cord injury, stroke, amyotrophic lateral sclerosis and other neurodegenerative diseases) and will expand their use for the treatment of other organs.
Almost 15 years ago, Evan Snyder and his group discovered that inflammation signals stem cells about damage and attracts them. However, it is impossible to use inflammation as a bait, since it can worsen the condition of the entire body. Thus, scientists were looking for tools that would help stem cells migrate to damaged tissues. This tool would be useful in neurological disorders in which inflammatory signals disappear over time, for example, in chronic spinal cord injury or stroke, as well as in conditions in which the role of inflammation is not fully understood, for example, in heart disease.
Snyder's group has developed a drug that can increase the ability of stem cells to accumulate in the damaged area and initiate the restoration of nerve tissue.
Only useful properties
In the course of the study, scientists modified the chemokine CXCL12, which Snyder's group had previously discovered and which can direct stem cells to tissues in need of repair. The resulting substance SDV1a binds more intensively to stem cells and has minimal inflammatory activity. In other words, it is able to lure stem cells to a specific location without causing unwanted inflammation.
To demonstrate that the new drug increases the effectiveness of stem cell treatment, the researchers implanted SDV1a and human stem cells into the brains of mice with Sandhoff's disease. This is a neurodegenerative disease in which intense microgliosis occurs with the accumulation of toxic metabolites GM2 and GA2, which gradually destroy the central nervous system and lead to the death of the body.
On the left is a slice of the cerebral cortex of a mouse with Sandhoff's disease without treatment. Cells with increased expression of proteins that enhance microgliosis and the progression of neurodegeneration are colored green. On the right is the brain of a mouse with the same disease that received therapeutic stem cells (red) and the drug SDV1a; the toxic cells disappeared.
This experiment showed that SDV1a helps human stem cells migrate and realize therapeutic effects, including increasing life expectancy, delaying the onset of symptoms and maintaining motor function much longer than in mice who did not receive the drug. It is important to note that the inflammation was not activated, and the stem cells were able to suppress the pre-existing inflammation.
Next steps
Researchers have already begun testing the ability of SDV1a to improve stem cell therapy on a mouse model of amyotrophic lateral sclerosis, which is caused by the progressive death of motor neurons in the brain. Previous studies conducted by Snyder's group have shown that the accumulation of stem cells helps more motor neurons survive, so scientists hope that SDV1a will increase the number of stem cells and help slow the onset and progression of the disease.
The authors believe that the new drug will help not only with neurodegenerative diseases, but also with damage to other organs – myocardial infarction, stroke, arthrosis and even brain cancer.
Article by J.P.Lee et al. Chemical mutagenesis of a GPCR ligand: Detoxifying “inflammo-attraction" to direct therapeutic stem cell migration is published in the journal PNAS.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on SBP: World's first: Drug guides stem cells to desired location, improving their ability to heal.