The intravenous infusion of mesenchymal stem cells from family donors is safe and improves symptoms such as pruritus (itching), sleep disturbances, and fatigue associated with Recessive Dystrophic Epidermolysis Bullosa (RDEB), popularly known as "butterfly skin". This is one of the primary conclusions of a clinical trial conducted by researchers from the Universidad Carlos III de Madrid (UC3M), the Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) of the Ministry of Science, Innovation and Universities, the Fundación Jiménez Díaz Health Research Institute (IIS-FJD), the CIBER Rare Diseases (CIBERER), and the La Paz University Hospital in Madrid.
The research team has also identified two biomarkers that make it possible to predict which individuals will show a more favorable clinical response to this advanced therapy treatment. “The infused mesenchymal stem cells act as regulators of the immune system, helping to control the state of permanent inflammation that deteriorates the health and well-being of patients,” explains the study's lead investigator, Dr. María José Escámez, a researcher at CIBERER-ISCIII and IIS-FJD. According to the team, the results are encouraging: after receiving three infusions, the eight pediatric patients who completed the study showed an overall reduction in pruritus, improved sleep quality, and lower levels of fatigue.
Butterfly skin is a rare and high-impact genetic disease characterized by extreme fragility of the skin and mucous membranes, causing blisters and wounds at the slightest touch. Furthermore, it is associated with a systemic chronic inflammatory response that impairs quality of life and affects life expectancy. According to scientific sources, it currently affects approximately 500,000 people worldwide.
The study, recently published in the journal Frontiers in Immunology, received funding from the Institute of Health Carlos III (ISCIII, by its acronym in Spanish), the Spanish State Research Agency (AEI, by its acronym in Spanish), and the patient associations DEBRA-Spain and Berritxuak. Additionally, the participation of the Complutense University of Madrid (UCM) and the Gregorio Marañón General University Hospital—in collaboration with Great Ormond Street Hospital in London—was fundamental in integrating clinical and scientific expertise into the study's development.
Mesenchymal stem cells are primarily found in the connective tissue (stroma) of bone marrow, adipose tissue (fat), and the umbilical cord. Generally, they possess a high immunomodulatory capacity and the ability to secrete repair factors, making them key in regenerative medicine and widely studied for treating inflammatory and degenerative diseases.
New hope for soothing inflammation
This clinical trial, named MesenSistem-EB (Phase I/II), evaluated the use of bone marrow-derived mesenchymal stem cells from family (haploidentical) donors. Unlike other approaches, this study did not seek solely to replenish collagen 7 (C7), but rather to act upon the patient's immune system.
The results of this study have confirmed the safety of this treatment, demonstrating that it is well-tolerated by pediatric patients with no serious adverse events associated with the infusion. Furthermore, the research team managed to stabilize systemic inflammation indicators (such as CRP and fibrinogen), ensuring that the patients' condition did not worsen during the one-year follow-up period.
The researchers identified two biomarkers, the molecules MCP1 and sCD40L, whose blood levels allow for the prediction of which patients will respond best to the treatment. “This represents an important step toward personalized medicine in rare diseases,” notes Marcela Del Río Nechaevsky, a researcher at the UC3M Department of Bioengineering and the IIS-FJD.
The value of public and social collaboration
The research team highlights that this breakthrough would not have been possible without a robust collaborative ecosystem. The project was funded by the ISCIII and the AEI, demonstrating the social return on public investment in science.
The role of the patient associations DEBRA-Spain and Berritxuak is of particular relevance, as they co-funded and supported the clinical trial from its inception. "For families, seeing science advance in the control of pain, itching, and sleep quality is a beacon of hope. This treatment doesn't just treat the skin; it treats the daily lives of children," the associations stated.
The researchers conclude that this therapeutic approach could become a fundamental complementary strategy to mitigate inflammatory escalation during critical phases of the disease. “The MesenSistem-EB clinical trial lays the groundwork for future combined protocols that could transform the prognosis of butterfly skin internationally,” indicates another of the study's authors, Lucía Martínez Santamaría, a researcher at the UC3M Department of Bioengineering and the IIS-FJD.