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Omic-MesenSistem-EB, Metabolomic and transcriptomic integrated analysis to identify the therapeutic mechanisms of mesenchymal stromal cells in patients with recessive dystrophic epidermolysis bullosa

Project lead MJ Escámez
Organisation CIEMAT - Centro de Investigaciones Energéticas Medioambientales y Tecnológicas, Madrid, SPAIN
Partner organizations & collaborators UC3M – Universidad Carlos III de Madrid
Project budget EUR 43,000.00
Start date / Duration 01. Jan 2018 / 36 months
Funder(s) / Co-Funder(s) Others
Other funder(s) CIBER on Rare Diseases - Carlos III Health Institute and European Regional Development Fund (CIBERER-ISCIII-ERDF)
Research area EB genetics, epigenetics & biology, Cellular therapy

Project details

Short lay summary

People with recessive dystrophic epidermolysis bullosa (RDEB) get wounds and blisters and other complications linked to inflammation. There are no medications to cure epidermolysis and, therefore, doctors and scientists are investigating new medications. Mesenchymal stromal cells (MSC) are one of the new medication investigated in the MesenSistem-EB trial at La Paz hospital. Children with epidermolysis treated with MSC, in the United Kingdom and in Egypt improved the disease a little and only for a while. This project will investigate how exactly MSC do their function using very modern and powerful tools of molecular biology and computer tools, called transcriptomics and metabolomics. The transcriptomics and the metabolomics will help to know how genes and other substances called metabolites (found in the blood, urine or blister fluid) behave after treatment with MSCs. Understanding this, could be helpful to predict if the medication will work for a patient and to find a way to make the medication work better or for a longer time.

Scientific summary

Recessive dystrophic bullosa epidermolysis (EBDR) is a low prevalence, chronically disabling and potentially lethal genodermatosis that has no cure. Two recent clinical trials have demonstrated a temporary therapeutic benefit in patients with EBDR following systemic administration of allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs). However, the mechanisms by which MSCs mediate their therapeutic effect are unknown. This project is a sub-study nested to the clinical trial MesenSistem-EB, whose objective is to provide more safety data on the systemic administration of BM-MSC in EBDR and assess whether haploidentical cells can be better tolerated and yield additional benefits. The objective of this project is to understand the mechanical aspects by which MSCs exert their therapeutic effect, in the unique context provided by the clinical trial, combining transcriptomic (RNA-Seq) and metabolomic (MS and NMR) massive analysis techniques. The analysis of the transcriptome modulation will be performed on skin biopsies and the variation in the metabolic profile on different biological fluids (urine, serum and blister fluid). Samples from 9 RDEB pediatrics patients obtained before and after treatment will be used.

Strategic relevance

The identification of transcriptomic and metabolic profiles could be key in predicting the outcome of patient’s condition and the individual's response to MSCs. Furthermore, describing the interactions between genes and metabolites would provide an integrated image of the molecular response in the skin and at systemic level in RDEB. Results may raise solid hypotheses about the mechanisms of action of MSCs that could result in the optimization of treatment as well as the development of new ones.


recessive dystrophic epidermolysis bullosa
systemic cell therapy
mesenchymal stromal cells
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