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

Autor: Song-Ee Kim, Sang Eun Lee, Soo Chan Kim, Boyoung Cho, Kinam Kim, Kyounghwan Roh, Seung-Ju Lee
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
Severity of Illness Index
Umbilical cord
Gastroenterology
0302 clinical medicine
Clinical endpoint
Child
Infusions
Intravenous
Skin
Pain Measurement
Dermoepidermal junction
Stem cell transplantation
General Medicine
Middle Aged
Allografts
Epidermolysis Bullosa Dystrophica
C-Reactive Protein
Treatment Outcome
medicine.anatomical_structure
030220 oncology & carcinogenesis
Systemic administration
Medicine
Female
Cord Blood Stem Cell Transplantation
Epidermolysis bullosa
Genetic diseases
Adult
medicine.medical_specialty
Collagen Type VII
Adolescent
Mucocutaneous zone
Genes
Recessive
Dermatology
Mesenchymal Stem Cell Transplantation
Young Adult
03 medical and health sciences
Internal medicine
medicine
Humans
Clinical Trials
Adverse effect
business.industry
Pruritus
Mesenchymal stem cell
medicine.disease
030104 developmental biology
Mutation
Clinical Medicine
business
Zdroj: JCI Insight
JCI Insight, Vol 6, Iss 2 (2021)
ISSN: 2379-3708
DOI: 10.1172/jci.insight.143606
Popis: BACKGROUND Recessive 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. METHODS Four 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. RESULTS Intravenous 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. CONCLUSION To 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 REGISTRATION ClinicalTrials.gov NCT04520022. FUNDING This work was supported by Daewoong Pharmaceutical Co. Ltd. and Kangstem Biotech Co. Ltd.
Databáze: OpenAIRE
Externí odkaz: