RDEB is an incurable rare blistering disorder due to a lack of collagen VII, causing mucocutaneous damage complicated with systemic inflammation. Mesenchymal stromal cells (MSC) have immunomodulatory, antinflammatory and tissue-regenerative properties. Four clinical trials of intravenous MSC in RDEB, one of them by us (Mesensistem-EB, NCT04153630), found temporary clinical benefits but the therapeutic mechanism remain elusive. We have reported the regulation of MCP1 and TGFβ correlating with the health improvement of an RDEB patient after systemic MSC. We have explored this matter in the context of Mesensistem-EB in which 8 RDEB paediatric patients were treated with 3 intravenous injections (2-3 millions of MSC/kg/infusion) separated by 21 days. Elevated MCP1 levels in 5 of the patients normalized in 4 of them for one year; while levels were steadily normal in the other 3 patients before and after treatment. In this cohort, TGFβ levels were normal in 7 children and without suffering global or individual relevant changes after the treatment. However, the level of a profibrotic member of the TNF family, sCD40L, normalized alongside MCP1 in the same 5 individuals after MSCs. Moreover, C Reactive Protein levels and EBDASI were improved or stabilized after the treatment in 4 of these patients. Thus, normalization of MCP1, by down or up-regulating it levels might be a relevant event in the therapeutic action of MSC valuable to be further explored.

RDEB is an incurable rare blistering disorder due to a lack of collagen VII, causing mucocutaneous damage complicated with systemic inflammation. Mesenchymal stromal cells (MSC) have immunomodulatory, antinflammatory and tissue-regenerative properties. Four clinical trials of intravenous MSC in RDEB, one of them by us (Mesensistem-EB, NCT04153630), found temporary clinical benefits but the therapeutic mechanism remain elusive. We have reported the regulation of MCP1 and TGFβ correlating with the health improvement of an RDEB patient after systemic MSC. We have explored this matter in the context of Mesensistem-EB in which 8 RDEB paediatric patients were treated with 3 intravenous injections (2-3 millions of MSC/kg/infusion) separated by 21 days. Elevated MCP1 levels in 5 of the patients decreased towards normalization in 4 of them for one year; while levels were steadily normal in the other 3 patients before and after treatment. In this cohort, active TGFβ levels were low or normal and without suffering global or individual relevant changes after the treatment. However, the level of a profibrotic member of the TNF family, sCD40L, normalized alongside MCP1 in the same 4 individuals after MSCs. Moreover, C Reactive Protein levels and EBDASI were improved or stabilized after the treatment in 4 of these patients. Thus, normalization of MCP1, by down or up-regulating it levels might be a relevant event in the therapeutic action of MSC valuable to be further explored.

ESDR281 - Normalization of MCP1 and sCD40L after systemic treatment with bone marrow derived mesenchymal stromal cells correlated with clinical benefits in patients with recessive dystrophic epidermolysis bullosa

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.