Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system (CNS). Among the diverse immune and stromal populations that orchestrate disease initiation and evolution, macrophages are central conductors of both tissue injury and repair. Depending on cues from their microenvironment, macrophages can amplify demyelinating inflammation or switch toward pro-resolving programs that foster debris clearance and remyelination. Understanding and modulating these macrophage states is therefore pivotal for next-generation MS therapies and for translational models that accurately predict clinical outcomes.

Creative Biolabs has established a comprehensive, industry-leading platform of in vivo and in vitro models to specifically interrogate the role of macrophages and microglia in MS pathogenesis and repair.

Functions of Macrophages in MS

Reactive macrophages can mediate cell injury or neuroprotective effects in MS, and they promote the relapsing-remitting feature of MS. During the acute phase, macrophages become the M1 macrophages immediately after activation, and they potentially release a large number of proinflammatory cytokines, which are thought to induce tissue damage, demyelination, and neuronal death in the CNS. The M2 macrophages undergo a gradual increase during the process of inflammation until the peak of disease, whereas the amount of M1 macrophages is decreased. During the later phase, M2 macrophages are predominant in the CNS, where they can release a variety of anti-inflammatory cytokines such as interleukin 13 (IL-13), IL-33, IL-4, IL-10, and transforming growth factorβ (TGFβ).

Fig.1 Roles of M1/M2 microglia and the effect of different drugs on these cells in MS.^1,3

Polarization of Macrophages in MS

Macrophage polarization is tuned by a network of signaling molecules, transcription factors, epigenetic mechanisms, and post-transcriptional regulators. M1 phenotype of macrophages can produce proinflammatory cytokines, chemokines, and nitric oxide (NO). Moreover, they show an increased ability to present antigens, cause phagocytic infections induced by bacterial, viral, or fungal factors, as well as kill tumor cells. Unlike M1 macrophages, M2 macrophages do not display any cytotoxic properties, they contribute to parasite clearance, and, in allergic reactions, they have functions related to tissue remodeling, angiogenesis promotion, tumor progression, and immunoregulation. M2-polarized macrophages are further subdivided into M2a, M2b, and M2c. Macrophages are multifunctional cells that do not stay in a constantly active state. In addition, they are often in the process of dynamically changing from M1 to M2, or the reverse, depending on the environment in which they live.

Featured MS-Focused Macrophage Services

Backed by our integrated macrophage therapeutics development platform, we offer MS-relevant services that span discovery to preclinical validation—customizable as standalone modules or one-stop programs.

Microglia & CNS-Associated Macrophage Analysis Services

• Primary & iPSC-derived human microglia: Generation, maturation, and QC (marker panels: TMEM119, P2RY12, TREM2, CX3CR1).
• BAM characterization: Perivascular/meningeal macrophage marker profiling (LYVE-1, MRC1, CD163).
• Multi-omic phenotyping: Flow, bulk RNA-seq, ATAC-seq; cytokine multiplexing.
• Metabolic assays: Seahorse XF (glycolysis, OXPHOS), mitochondrial membrane potential, lipidomics for myelin handling.

Macrophage Polarization & Function Assays

• Contextual polarization: IFN-γ/LPS (pro-inflammatory), IL-4/IL-13 (alternative), IL-10/TGF-β (pro-resolving), GM-CSF vs M-CSF paradigms.
• Functional readouts: Myelin phagocytosis (labeled myelin), antigen presentation (MHC-II, co-stimulatory molecules), ROS/NO, inflammasome activation (ASC speck assays, active caspase-1), efferocytosis.

BBB & Neurovascular Co-culture Systems

• Human iPSC-BBB models: Endothelial cells with pericytes and astrocytes; TEER measurement; live imaging of monocyte transmigration.
• Endothelial activation panels: VCAM-1/ICAM-1 induction, chemokine gradients (CCL2/CXCL10), and permeability (FITC-dextran) assays.

Antigen Processing & T-Cell Co-culture Platforms

• Myelin antigen libraries: MBP, PLP, MOG peptide pools for uptake and presentation assays.
• Th1/Th17 licensing readouts: IL-17/IFN-γ/GM-CSF; T-cell proliferation and cytotoxicity indices.

Macrophage Reprogramming & Drug Delivery

• Gene network engineering: CRISPRa/i, shRNA, or lentiviral vectors to modulate TREM2, CSF1R, NR4A, PPARγ axes.
• Nanocarriers: Mannosylated liposomes, PLGA NPs, ligand-targeted exosomes; cargo options include SPMs, siRNA, and BTK/CSF1R-pathway modulators.
• Readouts: Target engagement, transcriptomic shifts, lipid processing competence, and remyelination permissiveness.

Each module can be tailored to your indication, species, and development stage—screening, MoA deconvolution, or IND-enabling studies.

Workflow

Macrophages as Therapeutic Targets in MS

Given the profound and dual role of macrophages and microglia, they represent one of the most exciting and complex therapeutic targets for the next generation of MS drugs.

• Inhibiting the inflammatory effector functions and blockade of M1 macrophages recruitment: by a variety of compounds such as teriflunomide, interferon β (IFN-β), glatiramer acetate, resveratrol, neuropeptide Y, valproic acid, tuftsin, and fasudil; by microRNAs; blocking antibodies for granulocyte-macrophage colony-stimulating factor (GM-CSF).
• Inhibiting the activation of macrophages: Ethyl pyruvate, IFN-β, glucocorticoids, glatiramer acetate, fingolimod.
• Augmentation and restoration of the anti-inflammatory phenotype M2 cells by Lenalidomide, spermidine, forskolin, estrogen.
• Depleting specific macrophages by Liposomes or nanoparticles.
• Macrophages can be used as cellular vehicles for the delivery of small drugs, RNAs, and proteins.
• Modulation of pro-remyelination via microglia. The retinoid X receptor (RXR) agonists hold promise to reverse deficiencies in phagocytosis and remyelination.

Fig.2 Proposed actions of disease-modifying MS therapies targeting macrophages.^{2, 3}

Our Capabilities: Advancing Your MS Research

Creative Biolabs is your dedicated partner for macrophage-centric MS research. Our end-to-end platform combines these sophisticated models with a state-of-the-art analytical laboratory to provide a complete, integrated solution.

Based on our comprehensive macrophage therapeutics platform, you can mix-and-match the above for MS programs.

Related Products

Browse a representative set of products commonly used in MS-focused myeloid research; contact us for the latest catalog and inventory.

Scientific Resources

Q & A

Q: How does Creative Biolabs model macrophage behavior in MS research?

A: We combine human iPSC-derived microglia, primary monocyte-derived macrophages, and BBB co-culture systems to replicate both infiltrating and resident macrophage populations. Our assays measure polarization markers, cytokine release, lipid metabolism, and efferocytosis using high-content imaging and multi-omics.

Q: Do you provide assays to study macrophage trafficking across the blood–brain barrier?

A: Absolutely. Creative Biolabs offers iPSC-derived human BBB models incorporating endothelial cells, astrocytes, and pericytes. We assess monocyte adhesion, transmigration, and barrier integrity under inflammatory conditions (e.g., CCL2, CXCL10 stimulation).

Q: Can you customize macrophage assays for progressive MS research?

A: Yes. We design tailored models that mimic chronic active lesions and smoldering rim pathology, incorporating iron metabolism, oxidative stress, and mitochondrial dysfunction. We evaluate markers like H-ferritin, TMEM119, TREM2, and C1q. These assays help clients dissect chronic neuroinflammation and evaluate therapies targeting progressive MS stages.

Q: Can Creative Biolabs help identify macrophage-related biomarkers for MS?

A: Yes. We provide comprehensive biomarker discovery and validation services, integrating proteomics, transcriptomics, and cytokine multiplex assays. Common biomarkers include sTREM2, chitotriosidase, osteopontin, and neurofilament light chain (in combination with myeloid signatures).

We'll assemble a fit-for-purpose macrophage program with the right human-relevant models and translational readouts to accelerate decision-making.

Ready to discuss an MS macrophage strategy? Contact Creative Biolabs to co-design your study plan and receive a tailored quote.

References

1. Radandish, Maedeh, Parvin Khalilian, and Nafiseh Esmaeil. "The role of distinct subsets of macrophages in the pathogenesis of MS and the impact of different therapeutic agents on these populations." Frontiers in Immunology 12 (2021): 667705. https://doi.org/10.3389/fimmu.2021.667705
2. Wang, Jiaying, et al. "Targeting microglia and macrophages: a potential treatment strategy for multiple sclerosis." Frontiers in Pharmacology 10 (2019): 286. https://doi.org/10.3389/fphar.2019.00286
3. Distributed under Open Access license CC BY 4.0, without modification.