Long-term efficacy and safety of intravenous injection of clonal mesenchymal stem cells derived from bone marrow in five adults with moderate to severe atopic dermatitis.

Atopic dermatitis is a chronic and relapsing inflammatory skin disease that is treated with immunosuppressants. However, long-term use of immunosuppressants may cause toxicity and severe side-effects. To confirm the long-term efficacy and safety of clonal mesenchymal stem cell therapy, we performed investigator-initiated clinical trials and long-term observation in five adult patients with moderate to severe atopic dermatitis that was refractory to conventional treatments. The clinical response assessment values such as Eczema Area and Severity Index (EASI) improved significantly at 16 weeks, and 80% (4/5) of the patients achieved EASI-50 after one or two treatment cycles. Patients were observed for long-term efficacy and safety for an average of 38 weeks (range, 16-86) and showed no serious side-effects. Among the cytokines tested, CCL-17, interleukin (IL)-13, and IL-22 significantly decreased at the end-point of the five participants, two patients who maintained good clinical response over 84 weeks showed increased IL-17 cytokine levels in the blood.

Repeated ultraviolet irradiation induces the expression of Toll-like receptor 4, IL-6, and IL-10 in neonatal human melanocytes.

BACKGROUND: Human melanocytes express Toll-like receptor 4 (TLR4), which regulates ultraviolet (UV)-induced cutaneous immunosuppression in Langerhans cells. Lipopolysaccharide (LPS) stimulation increases melanocyte pigmentation and TLR4 expression, while inducing local innate inflammatory responses. AIMS: We investigated whether UV radiation induces TLR4 expression in neonatal human melanocytes (NHMs) and how this affects the immune system. METHODS: We cultured NHMs with LPS treatment or with one-time or repeated UVA or UVB exposure, and investigated and compared the effects on TLR4 expression, melanin contents, and cytokine production. RESULTS: NHMs in the resting state did not express TLR4. LPS stimulation induced TLR4 expression and increased pigmentation. TLR4 expression was not detected after single-dose UVA or UVB treatment, but pigmentation increased. Repeated UV treatment induced TLR4 expression and increased pigmentation. LPS stimulation and repeated UV treatment increased IL-6 secretion, and repeated UVB treatment increased IL-10 secretion. CONCLUSION: These results suggest that human melanocytes may actively participate in UV-induced immune modulation.