D3.387 - Assessment of safety of cryopreserved mesenchymal stem cells in the treatment of atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease which significantly reduces the quality of  life. AD treatment aims to minimize symptoms and flares. Mesenchymal stem cells (MSCs) possess strong immunomodulatory and regenerative properties possibly useful for AD treatment. Cryopreserved MSCs would reduce the cultivation time and cost of therapy. The aim of the current study was to assess the safety and tolerability of cryopreserved MSCs in the treatment of AD.

MSCs were obtained from the biopsies of olfactory mucosa (OM) of donors (negative for HBV, HCV, HIV, VZV, HSV-1, HSV-2, Parvovirus B19, CMV, HVV-6) and cultured at standard conditions (37°C, 5% CO2). Allogenic OM-MSCs-CD90⁺ CD105⁺ CD73⁺ HLA-DR^- CD31^-CD45^- were cryopreserved in medium containing 93% human AB serum and 5% DMSO using step-by-step cell freezing protocol: 2 hours at +4°С, 2 hours at –25°С and transfer to freezer at –80°С for long-term storage. After 2-3 weeks of storage 1 ampule of MSCs from a batch was tested for immunosuppressive properties. Suppression of the proliferation of T cells stimulated by PHA (at least 70% compared to control) and viability using 7AAD (at least 80%) were assessed. Before use, cryo-MSCs were thawed in a 37 °C water bath, followed by centrifugation and resuspended in NaCl. A single dose of cryo-MSCs contained 5 millions of cells.

A  group of patients with local and diffuse AD (n=6)  received treatment using standard clinical protocols plus local subcutaneous injections of cryo-MSCs (3-8 doses) into affected areas. The tolerability of subcutaneous injections of cryo-MSCs was assessed. No general (increased body temperature, changes in heart rate, blood pressure, immediate allergic reactions) and no local reactions (pain, itching, inflammation) were observed. Allergic reactions were also not detected. Patients noted good tolerability of the procedure, the absence of adverse pain reactions at the time of administration and after the use of MSCs.

Cryo-OM-MSCs as  adjuvant therapy for AD was safe and well tolerated. Clinical trials are ongoing and the group of AD patients is expanding with clinical and immunologic efficacy assessment currently in process.