{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T23:32:59Z","timestamp":1793748779335,"version":"4.6.1"},"reference-count":50,"publisher":"American Society for Clinical Investigation","issue":"2","license":[{"start":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T00:00:00Z","timestamp":1611532800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,25]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>\n                      Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable disease that causes severe mucocutaneous fragility due to mutations in\n                      <jats:italic>COL7A1<\/jats:italic>\n                      (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\u2013derived mesenchymal stem cells (hUCB-MSCs) in patients with RDEB.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Four adult and two pediatric patients with RDEB were treated with 3 intravenous injections of hUCB-MSCs (1 \u00d7 10\n                      <jats:sup>6<\/jats:sup>\n                      to 3 \u00d7 10\n                      <jats:sup>6<\/jats:sup>\n                      cells\/kg) every 2 weeks and followed up for 8\u201324 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>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\u2013112 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT04520022.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>This work was supported by Daewoong Pharmaceutical Co. Ltd. and Kangstem Biotech Co. Ltd.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci.insight.143606","type":"journal-article","created":{"date-parts":[[2021,1,24]],"date-time":"2021-01-24T14:01:40Z","timestamp":1611496900000},"source":"Crossref","is-referenced-by-count":56,"title":["Intravenous allogeneic umbilical cord blood\u2013derived mesenchymal stem cell therapy in recessive dystrophic epidermolysis bullosa patients"],"prefix":"10.1172","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4720-9955","authenticated-orcid":true,"given":"Sang Eun","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology Research Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6027-8659","authenticated-orcid":true,"given":"Seung-Ju","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology Research Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7369-7310","authenticated-orcid":true,"given":"Song-Ee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology Research Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinam","family":"Kim","sequence":"additional","affiliation":[{"name":"Cellular Therapeutics Team, Daewoong Pharmaceutical Co. Ltd., Seoul, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyoung","family":"Cho","sequence":"additional","affiliation":[{"name":"Cellular Therapeutics Team, Daewoong Pharmaceutical Co. Ltd., Seoul, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5797-148X","authenticated-orcid":true,"given":"Kyounghwan","family":"Roh","sequence":"additional","affiliation":[{"name":"Department of Clinical Development, Kangstem Biotech Co. Ltd., Seoul, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-Chan","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2021,1,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.18921"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2009.03.052"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2009.03.053"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2018.4673"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0910501"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.12599"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2013.08.014"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2015.158"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/dth.12305"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2018.04.028"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2907"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2020.05.078"},{"issue":"19","key":"B13","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.130554","article-title":"Phase 1\/2a clinical trial of gene-corrected autologous cell therapy for recessive dystrophic epidermolysis bullosa","volume":"4","author":"Eichstadt","year":"2019","journal-title":"JCI Insight"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2019.11.038"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3727\/096368913X663569"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1966"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.23042"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2015.2413"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2015.03.612"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2017.1316713"},{"key":"B21","doi-asserted-by":"crossref","DOI":"10.12688\/f1000research.20002.1","article-title":"Past, present, and future efforts to enhance the efficacy of cord blood hematopoietic cell transplantation","volume":"8","author":"Huang","year":"2019","journal-title":"F1000Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2005-0342"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3390\/ijms140917986"},{"key":"B24","doi-asserted-by":"crossref","DOI":"10.1016\/j.eclinm.2019.100249","article-title":"Cell therapy with intravascular administration of mesenchymal stromal cells continues to appear safe: an updated systematic review and meta-analysis","volume":"19","author":"Thompson","year":"2020","journal-title":"EClinicalMedicine"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/path.4133"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.02.015"},{"key":"B27","doi-asserted-by":"crossref","DOI":"10.1038\/srep38308","article-title":"Human mesenchymal stem cells program macrophage plasticity by altering their metabolic status via a PGE2-dependent mechanism","volume":"6","author":"Vasandan","year":"2016","journal-title":"Sci Rep"},{"key":"B28","doi-asserted-by":"crossref","DOI":"10.1155\/2019\/7132708","article-title":"MSC-derived exosome promotes M2 polarization and enhances cutaneous wound healing","volume":"2019","author":"He","year":"2019","journal-title":"Stem Cells Int"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-019-1999-8"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12622"},{"key":"B31","doi-asserted-by":"crossref","DOI":"10.3389\/fncel.2019.00422","article-title":"Mast cells and sensory nerves contribute to neurogenic inflammation and pruritus in chronic skin inflammation","volume":"13","author":"Siiskonen","year":"2019","journal-title":"Front Cell Neurosci"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12152"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000001528"},{"issue":"10","key":"B34","doi-asserted-by":"crossref","DOI":"10.3390\/ijms17101625","article-title":"Autoimmunity and cytokine imbalance in inherited epidermolysis bullosa","volume":"17","author":"Esposito","year":"2016","journal-title":"Int J Mol Sci"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-0376"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.det.2010.01.008"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.12885"},{"key":"B38","doi-asserted-by":"crossref","unstructured":"Papanikolaou M, et al. Prevalence, pathophysiology and management of itch in epidermolysis bullosa [published online August 18, 2020]. Br J Dermatol. https:\/\/doi.org\/10.1111\/bjd.19496","DOI":"10.1111\/bjd.19496"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.5021\/ad.2016.28.1.6"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1197\/S1069-6563(03)00372-5"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-2433"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2014.500"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx069"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.15905"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.16363"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2019.09.014"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2018.12.005"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1398-3"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1484-6"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2018.04.007"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/143606\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:49:25Z","timestamp":1779151765000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/143606"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,25]]},"references-count":50,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,1,25]]},"published-print":{"date-parts":[[2021,1,25]]}},"alternative-id":["10.1172\/jci.insight.143606"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.143606","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,25]]},"article-number":"e143606"}}