Intravenous allogeneic umbilical cord blood–derived mesenchymal stem cell therapy in recessive dystrophic epidermolysis bullosa patients

• DOI: 10.1172/jci.insight.143606
• Publication Date: 2021-01-24T19:01:40Z
• Authors: Sang Eun Lee; Seung-Ju Lee; Song-Ee Kim; Kinam Kim; Boyoung Cho; Kyounghwan Roh; Soo-Chan Kim
• Keywords: Male; Severity of Illness Index; Clinical trials; 0302 clinical medicine; Epidermolysis Bullosa Dystrophica / therapy*; Child; Infusions, Intravenous; Cord Blood Stem Cell Transplantation / methods; Skin; Pain Measurement; Mesenchymal Stem Cell Transplantation / methods*; Cord Blood Stem Cell Transplantation / adverse effects; Stem cell transplantation; R; Epidermolysis Bullosa Dystrophica / genetics; Middle Aged; Allografts; Epidermolysis Bullosa Dystrophica; 3. Good health; C-Reactive Protein; Treatment Outcome; Medicine; Female; Cord Blood Stem Cell Transplantation; Intravenous; Genetic diseases; Adult; Infusions; Collagen Type VII; Adolescent; 610; Genes, Recessive; Dermatology; Mesenchymal Stem Cell Transplantation; Young Adult; 03 medical and health sciences; Recessive; Humans; Clinical Trials; Mesenchymal Stem Cell Transplantation / adverse effects; Pruritus / therapy; Pruritus; Epidermolysis Bullosa Dystrophica / pathology; Collagen Type VII / genetics; C-Reactive Protein / metabolism; Genes; Mutation; Clinical Medicine

BACKGROUNDRecessive dystrophic epidermolysis bullosa (RDEB) is an incurable disease that causes severe mucocutaneous fragility due to mutations in COL7A1 (encoding type VII collagen [C7]). In this phase I/IIa trial, we evaluated the safety and possible clinical efficacy of intravenous infusion of allogeneic human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in patients with RDEB.METHODSFour adult and two pediatric patients with RDEB were treated with 3 intravenous injections of hUCB-MSCs (1 × 106 to 3 × 106 cells/kg) every 2 weeks and followed up for 8-24 months after treatment. The primary endpoint was safety. Secondary endpoints related to efficacy included clinical parameters, such as disease severity score, wound assessment, itch and pain score, and quality of life. C7 expression levels and inflammatory infiltrates in the skin, as well as serum levels of inflammatory markers and neuropeptides, were also assessed.RESULTSIntravenous hUCB-MSC infusions were well tolerated, without serious adverse events. Improvements in the Birmingham Epidermolysis Bullosa Severity Score, body surface area involvement, blister counts, pain, pruritus, and quality of life were observed with maximal effects at 56-112 days after treatment. hUCB-MSC administration induced M2 macrophage polarization and reduced mast cell infiltration in RDEB skin. Serum levels of substance P were decreased after therapy. Increased C7 expression was observed at the dermoepidermal junction in 1 of 6 patients at day 56.CONCLUSIONTo the best of our knowledge, this is the first clinical trial of systemic administration of allogeneic hUCB-MSCs in patients with RDEB, demonstrating safety and transient clinical benefits.TRIAL REGISTRATIONClinicalTrials.gov NCT04520022.FUNDINGThis work was supported by Daewoong Pharmaceutical Co. Ltd. and Kangstem Biotech Co. Ltd.