A backpack-based myeloid cell therapy for multiple sclerosis.
Neha KapateMichael DunneNinad KumbhojkarSupriya PrakashLily Li-Wen WangAmanda GravelineKyung Soo ParkVineeth Chandran SujaJuhee GoyalJohn R CleggSamir MitragotriPublished in: Proceedings of the National Academy of Sciences of the United States of America (2023)
Multiple sclerosis (MS) is an incurable autoimmune disease and is currently treated by systemic immunosuppressants with off-target side effects. Although aberrant myeloid function is often observed in MS plaques in the central nervous system (CNS), the role of myeloid cells in therapeutic intervention is currently overlooked. Here, we developed a myeloid cell-based strategy to reduce the disease burden in experimental autoimmune encephalomyelitis (EAE), a mouse model of progressive MS. We developed monocyte-adhered microparticles ("backpacks") for activating myeloid cell phenotype to an anti-inflammatory state through localized interleukin-4 and dexamethasone signals. We demonstrate that backpack-laden monocytes infiltrated into the inflamed CNS and modulated both the local and systemic immune responses. Within the CNS, backpack-carrying monocytes regulated both the infiltrating and tissue-resident myeloid cell compartments in the spinal cord for functions related to antigen presentation and reactive species production. Treatment with backpack-monocytes also decreased the level of systemic pro-inflammatory cytokines. Additionally, backpack-laden monocytes induced modulatory effects on T H 1 and T H 17 populations in the spinal cord and blood, demonstrating cross talk between the myeloid and lymphoid arms of disease. Backpack-carrying monocytes conferred therapeutic benefit in EAE mice, as quantified by improved motor function. The use of backpack-laden monocytes offers an antigen-free, biomaterial-based approach to precisely tune cell phenotype in vivo, demonstrating the utility of myeloid cells as a therapeutic modality and target.
Keyphrases
- dendritic cells
- multiple sclerosis
- bone marrow
- acute myeloid leukemia
- immune response
- single cell
- spinal cord
- cell therapy
- peripheral blood
- mouse model
- induced apoptosis
- anti inflammatory
- mass spectrometry
- randomized controlled trial
- ms ms
- drug induced
- risk factors
- high dose
- quality improvement
- endothelial cells
- toll like receptor
- oxidative stress
- signaling pathway
- skeletal muscle
- case report
- high fat diet induced
- cerebrospinal fluid