Use of Mesenchymal Stem Cells to Treat Atopic Dermatitis

Use of Mesenchymal Stem Cells to Treat Atopic Dermatitis

Allergic diseases are immune-mediated diseases. Allergic asthma, allergic skin diseases, allergic rhinitis and allergic conjunctivitis are the most prevalent allergic diseases. The general common pathogenesis is the imbalance of the T lymphocytes Th1/Th2.

What Is Atopic Dermatitis? 

Atopic dermatitis (AD) or eczema is a condition that makes your skin red and itchy. It’s common in children but can occur at any age. Atopic dermatitis is a chronic condition and tends to flare periodically. It may be accompanied with other diseases like asthma and hay fever.

Children with atopic dermatitis often have skin barrier dysfunction which causes dry, itchy, scaly skin. They can also have associated environmental and food allergies.  Of children who have atopic dermatitis, 65 percent show signs in the first year of life and 90 percent show signs within the first five years. Half of all affected children improve between ages 5 and 15. Parents with atopic dermatitis are more likely to have children with atopic dermatitis.

About 17.8 million people have atopic dermatitis. Statistics from the National Eczema Association show how common the condition is. The prevalence of childhood atopic dermatitis is 10.7% in the US. Approximately one in three children with atopic dermatitis has a moderate to severe form.

Common Symptoms

Signs and symptoms vary widely from person to person and include:

  • Dry skin.
  • Itching.
  • Red to brownish-gray patches, especially on the hands, feet, ankles, wrists, neck, upper chest and eyelids.
  • Small raised bumps, which may leak fluid and crust over when scratched.
  • Thickened skin.
  • Swollen skin from scratching.

What Causes Atopic Dermatitis? 

Healthy skin helps retain moisture and protects you from bacteria, irritants and allergens. Eczema is related to a gene variation that affects the skin’s ability to provide this protection. This allows your skin to be affected by environmental factors, irritants and allergens.

The exact cause of Atopic dermatitis is unknown. Inflammation results from the presence of too many inflammatory cells in the skin. There’s evidence that people with atopic dermatitis have a compromised skin barrier compared to normal skin. Because the skin barrier is altered, they have drier skin. 

How is it Treated? 

The main treatment of this and other allergic diseases are symptomatic treatments including corticosteroids, antihistamines and antileukotrienes, which temporarily inhibit inflammatory mediators and immune cells. Caustative treatments such as desensitization and tolerance induction have also been applied.

Patients suffer from symptoms and signs due to the repetitive recurrence of the disease and the continuous medication use. Cyclosporin A and alkylating agents are used for refractory allergic diseases.

Other treatment options include:

  • Creams that control itching and help repair the skin.
  • Drugs to fight infection when present.
  • New options are monoclonal antibodies, like dupilumab (Dupixent), which is used to treat severe diseases that do not respond well to other treatment options.

Use of Cellular Therapies 

Mesenchymal stem cells (MSCs) are the major stem cells in the field of cell therapy. MSCs have been applied clinically for more than 10 years and have been proven to be safe and effective for autoimmune and inflammatory disorders.

Recently, MSCs therapy has been tried to treat allergic diseases. Atopic dermatitis is a good example of a systemic allergic skin disease.

MSCs can modulate the tissue repair process by differentiating into various types of cells. The type MSCs that have been investigated have come mostly from the umbilical cord, bone marrow and adipose tissue.  A number of recent studies have demonstrated that MSCs can also alleviate allergic immune disorders, such as asthma, allergic rhinitis and AD.

In 2014, the first successful MSCs therapy for AD was achieved in a mouse AD model. Stem cells from Bone marrow were used via intravenous administration. They showed suppression of cell infiltration in skin tissue and reduced IgE levels in serum, which are normally increased in allergic reactions. IL-4 expression in lymph nodes and cutaneous tissues was inhibited. MSCs inhibited B cell differentiation, T cell activities and cytokine production, which resulted in a beneficial effect.

Human Clinical Trials

In 2017, the first clinical trial of MSCT was conducted in AD as a phase I/IIa trial. Human umbilical cord blood-derived MSCs (hUCB-MSCs) were administered by subcutaneous injection with 2 × 107 as a lower dose and 5 × 107 as a higher dose for moderate to severe AD. A total of 37 patients were involved. Treatment was performed every 2 weeks for 12 weeks.

The treatment with hUCB-MSCs significantly decreased the clinical severity, according to the Eczema Area and Severity Index score, of 55% of patients. They had reduced serum IgE levels and blood eosinophil counts. No serious adverse events were reported. The study was the first to confirm the efficacy and safety of allogeneic MSCs for AD. There are 3 more clinical trials ongoing in Phase 1, 2 and 1/II.

Stem cell therapy is a promising and potent therapeutic modality for allergic disease in humans, especially those who don’t respond well to conventional treatments.

 

Sources: 

Kim, EY., Kim, H.S., Hong, KS. et al. Mesenchymal stem/stromal cell therapy in atopic dermatitis and chronic urticaria: immunological and clinical viewpoints. Stem Cell Res Ther 12, 539 (2021). https://doi.org/10.1186/s13287-021-02583-4.

Megan Baird (2017, Jun 12). What Is Atopic Dermatitis? Healthline. Retrieved from: healthline.com/health/atopic-dermatitis/what-is-atopic-dermatitis

https://www.mayoclinic.org/diseases-conditions/atopic-dermatitis-eczema/symptoms-causes/syc-20353273

https://www.childrenshospital.org/conditions-and-treatments/conditions/a/atopic-dermatitis-and-eczema/symptoms-and-causes#:~:text=The%20main%20triggers%20of%20atopic,t%20necessarily%20cause%20atopic%20dermatitis.

Image from: 

https://www.healthline.com/health/eczema/whats-the-difference-between-atopic-and-contact-dermatitis