M2 Macrophages in Therapy: The Body’s Defenders

Macrophages are a type of white blood cell that helps the immune system respond to infections and tissue damage. They are commonly known as “big eaters” due to their remarkable ability to engulf and destroy harmful invaders like bacteria, viruses, and dead cells. But beyond this, macrophages play an important role in the progression of inflammatory diseases.

How Macrophages Detect and Treat Inflammation

How do macrophages work? Monocytes, the precursors to macrophages, exit the bone marrow and enter the bloodstream. Once they detect an inflammation source, they migrate out of the bloodstream and into the affected tissues. Within the tissues, macrophages can differentiate into various forms depending on local growth factors, cytokines, and microbial products.

Macrophages Types and Their Specific

There are at least two primary functional subpopulations of macrophages: the “classical” proinflammatory M1 macrophages and the anti-inflammatory M2 macrophages. 

In the tissues, macrophages play several crucial roles, which helps to answer the question ‘how do macrophages work?’:

• Immune Regulation: They aid in immune regulation by releasing signaling molecules that attract other immune cells to the site of infection.
• Wound Healing: They assist in wound cleaning and encourage tissue repair.
• Inflammation: While excessive inflammation is harmful, it is necessary for the body’s protection. Macrophages play an important role in the inflammatory process, aiding in the control and resolution of inflammatory diseases such as diabetes, cancer, atherosclerosis, and central nervous system (CNS) disorders.
• Tissue Remodeling: They help to maintain tissue structure by removing old or damaged cells.

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Dr. Aleksandra Fetyukhina, MD

Medical Advisor, Swiss Medica doctor

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When Do We Use M2 Macrophages in Therapy

At Swiss Medica, we take a subset of macrophages from the patient’s bloodstream and polarize them all into M2 macrophages. Thus, they acquire anti-inflammatory properties and promote tissue repair and wound healing.

Properties of Μ2-type alternatively activated macrophages in the nervous system:

• Anti-inflammatory activity.
• Mediate neuroprotection.
• Activate neuro- and angio-genesis.
• Play an essential role in neuronal plasticity.
• Participate in axon remodelling.

The following are the conditions for which macrophage cell therapy is applicable:

1. Cerebral palsy (CP): A group of permanent movement disorders that appear in early childhood.
2. Stroke (outside acute phase): This category includes strokes that do not occur at the time of treatment.
3. Autism: A developmental disorder characterized by difficulties with social interaction, communication, and repetitive behaviors.
4. Liver cirrhosis: A late stage of scarring (fibrosis) of the liver caused by many forms of liver diseases and conditions, such as hepatitis and chronic alcoholism. 
5. Atherosclerosis: Plaques, which are composed of cholesterol, fatty deposits, cellular waste products, calcium, and fibrin, are produced as a result of this complex issue. They block and narrow arteries, making it difficult for blood to flow through.

In macrophage-based treatments, we typically use autologous cells. 

Macrophages Cell Collection and Preparation

We thoroughly test each treatment product several times before using it on a patient. With our in-house laboratory, we can closely monitor cells’ composition and viability, guaranteeing safe and effective doses.

There are three major stages for preparing cells before administration:

1st stage. For cell preparation, we collect blood—around 20 ml.

2nd stage. The macrophages are then polarized, which is the process of stimulating them to adopt a specific functional phenotype, in this case anti-inflammatory (M2), and secreted factors (Secretom / Exosomes). This preparation process takes 8–10 days.

3rd stage. Now in the laboratory, it is possible to cryopreserve macrophages and thaw 6 days before the patient arrives. This allows us to save them until the patient’s next visit and reduce treatment time.

If the patient’s own macrophages are not suitable for use, it is possible to utilize the secretome of macrophages from a relative, such as the child’s mother.

How Do We Deliver the Macrophages

We use two major approaches for the patient’s own macrophages and the exosomes:

• Intrathecal (directly into the spinal canal) or intravenous (into a vein) administration is performed with the patient’s own macrophages. 
• Exosomes derived from the patient’s cells or relatives are administered via nasal drops and given to the patient so that treatment can continue after they leave the clinic. 

Typically, macrophage cell therapy is used in conjunction with other regenerative methods, such as mesenchymal stromal cells and their derivatives.

Dosages

We take great care to measure the exact number of cells required for each individual case, leaving no room for error. The number of macrophages in samples from adults and children varies, ranging from 20 to 60 million cells. Because these cells are not cultured in the laboratory, the amount collected equals the amount given. Cells can be administered completely or partially frozen and stored until the patient’s next arrival.

Macrophage secretomes are provided in quantities of 20 vials, each containing 2 ml of secretion. They are used as part of maintenance therapy, which the patient continues to receive after discharge from the hospital.

Expected Time for Treatment Results

The treatment’s effects differ from person to person because it is used in conjunction with other procedures such as stem cell therapy, IMR, physiotherapy, and others. That’s why the answer to the question ‘How do macrophages work?’ may vary. For most conditions, the effect of therapy lasts from 1 to 3 months after starting the complex treatment. More information about expected outcomes for various conditions can be found on our dedicated page.

Safety of M2 Macrophages

A pilot study of M2 intrathecal administrations in 30 adults with ischemic stroke demonstrated safety and improved motor and cognitive functions.  There were no serious adverse events observed.

Another study of 21 children with cerebral palsy found no adverse events. During a 5-year follow-up, there were no cases of mortality, psychomotor deterioration, seizure exacerbation, or long-term comorbidities, including tumors.

However, there are two major serious challenges to this treatment. First and foremost, the invasive nature of intrathecal injection increases the risk of injection-related side effects. Second, the patient’s brain tissue may experience M2→M1 repolarization due to the pathological environment.

In this regard, the use of M2-derived soluble products (secretome/exosomes) instead of cells and intranasal administration appears to be a promising strategy. Exosomes ensure treatment safety because only their products are transported, not the M2 cells themselves (which can repolarize into M1 macrophages and cause inflammation). 

Side Effects of the Macrophages Therapy

When M2 macrophages are used, the therapy has no serious side effects. They do not pose a risk of inflammation following administration. Some side effects may occur during or following the complex treatment procedure, such as a brief fever or headaches that can be treated with pain relievers and rest.

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Get a no-obligation online consultation to learn about the benefits, costs, and duration of macrophage cell therapy for your case. Our medical advisors will create a personalized treatment plan and guide you through every step.

Dr. Aleksandra Fetyukhina, MD

Medical Advisor, Swiss Medica doctor

Your Name Please fill out this field Phone Please fill out this field E-mail Please fill out this field

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