Backpack-laden myeloid cells show promise for treating multiple sclerosis

Multiple Sclerosis (MS) is a devastating autoimmune disorder that damages the protective myelin coating surrounding nerves, disrupting the communication between the brain and body, leading to a gradual decline in physical and cognitive abilities. Shockingly, the MS atlas reported that a person is diagnosed with MS every five minutes globally, with around 2.8 million people currently living with the disease. Furthermore, the worldwide prevalence of MS has increased by 30% since 2013, indicating a concerning trend.

One of the primary culprits behind MS is the sudden inflammation of nerves caused by myeloid cells, belonging to the “innate” immune system, in vulnerable areas of the brain and spinal cord, which together form the central nervous system (CNS). These “acute inflammatory lesions” attract self-reactive T and B cells, part of the immune system’s “adaptive” arm, which attack the myelin covering.

Although there is no known cure for MS, available disease-modifying therapies come in the form of small molecule and protein drugs that either directly target the self-reactive immune cells or broadly suppress inflammation. However, many of these therapies have severe side effects on various parts of the body, including the immune system itself, making them risky to use.

Researchers at Harvard University’s Wyss Institute for Biologically Inspired Engineering and Harvard John A. Paulson School of Engineering and Applied Sciences have developed a promising new cell therapy for multiple sclerosis (MS). The therapy utilises myeloid cells, which are typically responsible for triggering the nerve inflammation that causes MS in patients.

The team developed a process that isolates and cultures monocytes from donor mice bone marrow and attaches tiny microparticles, known as “backpacks,” containing anti-inflammatory molecules to the cells’ surfaces. The backpacks are then able to guide the carrier cells’ differentiation into anti-inflammatory cells in vivo.

When the backpack-laden monocytes were infused back into mouse models of MS, the team found that they were able to affect MS-specific immune responses, partially reverse hind limb paralysis and improve motor functions. The results were published in the Proceedings of the National Academy of Sciences.

This new technique is simpler than other cell therapies, as myeloid cells can be easily obtained from peripheral blood and modified with backpacks within hours. This makes the therapy more easily translatable and suitable for treating CNS diseases, as some myeloid cell types can traverse the blood-brain barrier.

New spin for cellular backpacks

Previously, Mitragotri’s team discovered that backpacks attached to myeloid cells remained stable on the cell surface and could be controlled with specific molecules. They utilized this finding in a tumor-fighting therapy using backpack-laden macrophages. In their recent study, the team focused on monocytes, which can infiltrate the brain and differentiate into macrophages, a predominant inflammatory cell type in MS lesions. To control monocyte differentiation, they used backpacks loaded with interleukin-4 and dexamethasone, providing a synergistic anti-inflammatory effect. These micrometer-sized backpacks were created using a process called serial spin coating, where biocompatible substances and the anti-inflammatory molecules were layered on top of each other. Finally, an antibody fragment was added to the outer surface of the backpack to stick to monocytes.

Cellular backpacks get legs

The researchers conducted an experiment to evaluate the effectiveness of the backpack-laden monocytes as a therapy. They isolated monocytes from healthy donor mice and attached the backpacks to them after a short cell culture step. The modified cells were then infused into a mouse model of MS called experimental autoimmune encephalomyelitis (EAE).

The results of the experiment were encouraging, as the backpack-carrying monocytes infiltrated the inflamed CNS lesions more effectively than unaltered control monocytes. The anti-inflammatory monocytes reduced inflammation inside the lesions and shifted the local and systemic MS-associated immune response towards a therapeutic outcome. Moreover, the backpack-carrying monocytes elicited cross-talk effects with other immune cell populations, resulting in improved disease symptoms and extended survival rates.

The magnitude of therapeutic benefit observed was comparable to reported therapeutic treatments tested in other studies using the same EAE model. While the EAE model primarily mimics the progressive form of MS, the team intends to investigate their approach in models of relapsing-remitting MS, which is the more prevalent form of the disease. Suppressing inflammation early on could have immense benefits for patients.

The team’s ability to convert potentially pathogenic immune cells into therapeutic ones for MS could open up a new avenue for treating patients with various neurological diseases. Wyss Founding Director Donald Ingber commended the team’s achievement, stating that MS is an extremely hard or impossible disease to treat, and the new approach could provide hope to those suffering from the disease.

Source: Harvard University

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