Beneficial Effect of Systemic Allogeneic Adipose Derived Mesenchymal Cells on the Clinical, Inflammatory and Immunologic Status of a Patient With Recessive Dystrophic Epidermolysis Bullosa: A Case Report

Frontiers in Medicine

Alberto M. Borobia¹  Gustavo Melen²  Marta García³  Lucía Martínez-Santamaría³  Raúl de Lucas³  María del Carmen de Arriba³  Marta Carretero³  Nuria Illera³  Víctor Jiménez-Yuste⁴  Eva Jiménez⁶  Rosa Sacedón⁶  Rocío Maseda⁷  Isabel Pérez-Conde⁷  Sara García-Barcenilla⁸  Ángeles Vicente⁸  Nora Butta⁸  María José Escámez^1,10  Marcela del Río^1,10 

[1] Gene Therapies Laboratory, Niño Jesus University Hospital, Madrid, Spain;;Cell &Centre for Energy, Environment and Technology Research (CIEMAT), Madrid, Spain;Clinical Pharmacology Department, School of Medicine, La Paz University Hospital, IdiPAZ, Autonomous University of Madrid, Madrid, Spain;Department of Bioengineering, Carlos III University (UC3M), Madrid, Spain;Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain;Department of Dermatology, La Paz University Hospital, Madrid, Spain;Hematology Unit, La Paz University Hospital-IdiPAZ, Madrid, Spain;Rare Diseases Networking Biomedical Research Centre (CIBERER) U714, Madrid, Spain;Regenerative Medicine and Tissue Engineering Group, Health Research Institute Foundation of the Jiménez Díaz Foundation, Madrid, Spain;

关键词: recessive dystrophic epidermolysis bullosa (RDEB);    systemic cell therapy;    mesenchymal stromal cells (MSC);    inflammation;    case report;    adipose derived MSC (ADMSC);   

DOI  :  10.3389/fmed.2020.576558

来源: DOAJ

【 摘 要 】

Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable inherited mucocutaneous fragility disorder characterized by recurrent blisters, erosions, and wounds. Continuous blistering triggers overlapping cycles of never-ending healing and scarring commonly evolving to chronic systemic inflammation and fibrosis. The systemic treatment with allogeneic mesenchymal cells (MSC) from bone marrow has previously shown benefits in RDEB. MSC from adipose tissue (ADMSC) are easier to isolate. This is the first report on the use of systemic allogeneic ADMSC, correlating the clinical, inflammatory, and immunologic outcomes in RDEB indicating long-lasting benefits. We present the case of an RDEB patient harboring heterozygous biallelic COL7A1 gene mutations and with a diminished expression of C7. The patient presented with long-lasting refractory and painful oral ulcers distressing her quality of life. Histamine receptor antagonists, opioid analgesics, proton-pump inhibitors, and low-dose tricyclic antidepressants barely improved gastric symptoms, pain, and pruritus. Concomitantly, allogeneic ADMSC were provided as three separate intravenous injections of 106 cells/kg every 21 days. ADMSC treatment was well-tolerated. Improvements in wound healing, itch, pain and quality of life were observed, maximally at 6–9 months post-treatment, with the relief of symptoms still noticeable for up to 2 years. Remarkably, significant modifications in PBL participating in both the innate and adaptive responses, alongside regulation of levels of profibrotic factors, MCP-1/CCL2 and TGF-β, correlated with the health improvement. This treatment might represent an alternative for non-responding patients to conventional management. It seems critical to elucidate the paracrine modulation of the immune system by MSC for their rational use in regenerative/immunoregulatory therapies.

【 授权许可】

Unknown