Recessive dystrophic epidermolysis bullosa (RDEB) is one of the most severe skin diseases and is caused by loss-of-function mutations in COL7A1 encoding type VII collagen (C7). Patients with RDEB suffer since birth from skin and mucosal blistering and develop severe local and systemic complications resulting in a poor prognosis. Mesenchymal stromal cells (MSC) have been shown to have therapeutic potential to improve wound healing and skin inflammation in RDEB patients due to their capacity to express C7 and their anti-inflammatory properties. Clinical trials have shown transient improvement of RDEB patients with allogeneic MSC derived from healthy donor’s bone marrow (BM-MSC). The aim of this work is to optimize BM-MSC in vitro conditioning prior to their injection in murine models to improve their survival in the skin and mucosae. We first transduced healthy human BM-MSC with a fluorescent and bioluminescent reporter lentiviral vector with an efficiency of 60% without modifying their MSC phenotype. Transduced BM-MSC were cultured under hypoxic or normoxic conditions and were supplemented with either platelet lysate or foetal calf serum. BM-MSC were then injected subcutaneously (SC) or intravenously (IV) in immunodeficient mice. The behaviour of transduced BM-MSC upon their administration in mice was assessed using the bioluminescent reporter vector by means of in vivo imaging. After SC injection of BM-MSC, the bioluminescent signal remained localized to the site of injection for at least 7 months (ongoing monitoring). When BM-MSC were injected IV, the bioluminescence signal was not detected after 10 days. The optimization of in vitro conditioning and routes of administration of BM-MSC to improve their biodistribution and survival in murine models as assessed by in vivo imaging should contribute to develop efficient and persistent treatment of wounded skin and mucosae in the perspective of clinical translation for RDEB.

ESDR290 - Strategies to improve in vivo survival of Mesenchymal Stromal Cells after injection in immunodeficient mice

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.