Researchers at the Harvard Wyss Institute have developed a new type of cell therapy for multiple sclerosis patients. The technique involves taking a blood sample from the patient being treated, isolating a sample of myeloid white blood cells, and then modifying them with ‘backpacks’ that contain anti-inflammatory molecules. The modified cells can then be administered back to the patient, and the backpack ensures that they maintain an anti-inflammatory phenotype. The cells can access inflammatory lesions in the central nervous system that are characteristic of multiple sclerosis and help to reduce the inflammation and associated symptoms. In tests in a mouse model of MS, the cell therapy even helped to reduce the paralysis experienced by the mice, suggesting it has significant potential as a new treatment.
Multiple sclerosis (MS) is caused by dysfunctional myeloid cells, a type of white blood cell, that provoke inflammatory lesions in areas of the central nervous system. Current treatments have mixed efficacy and can have significant side-effects by suppressing inflammation generally. To address this, these researchers have turned the cells that can initiate MS into a cell therapy that can help to treat it.
The key behind the treatment lies in understanding that myeloid cells can exhibit anti- or pro-inflammatory states. Modifying them so that they stay in the anti-inflammatory state could help to reduce their role in contributing to MS and instead prime them to actually reduce inflammation in MS lesions in the central nervous system.
“Current MS therapies do not specifically target myeloid cells. These are very plastic cells that can toggle between different states and are thus hard to control. Our biomaterial-based backpack approach is a highly effective way to keep them locked into their anti-inflammatory state,” explains Samir Mitragotri, a researcher involved in the study. “In many ways simpler than other cell therapies, myeloid cells can be easily obtained from patients’ peripheral blood, modified with backpacks in a short culture step, and reinfused back into the original donor, where they find their way to inflammatory lesions and affect the MS-specific immune response not only locally, but more broadly.”
The technique involves isolating the cells from a patient’s blood and then modifying them by attaching a biomaterial ‘backpack’ containing anti-inflammatory molecules, such as dexamethasone, before re-administering them to the same patient. This process takes just a few hours, and so theoretically patients could have their cells isolated, modified, and re-administered all in the same day.
Excitingly, in mouse studies, the technique allowed mice with an experimental form of MS to overcome much of the paralysis they experienced in their hindlimbs, suggesting that the technology is a promising option for further development.
Backpack-carrying monocytes (right column), but not normal monocytes (middle column) or a salt solution (left column), when infused into a mouse model of multiple sclerosis (MS), prevent the invasion of inflammatory cells into “acute inflammatory lesions” (top row), and improve nerve myelination (bottom row). Credit: Wyss Institute at Harvard University.
Study in journal PNAS: A backpack-based myeloid cell therapy for multiple sclerosis