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Patients with RDEB suffer from recurrent erosions in skin and mucous membranes and have a high risk for developing cutaneous squamous cell carcinoma (cSCCs). TGF\u03b2 signaling has been associated with fibrosis and malignancy in RDEB. In this study, the activation of TGF\u03b2 signaling was demonstrated in col7a1\u2212\/\u2212 mice as early as a week after birth starting in the interdigital folds of the paws, accompanied by increased deposition of collagen fibrils and elevated dermal expression of matrix metalloproteinase (MMP)-9 and MMP-13. Furthermore, human cord blood-derived unrestricted somatic stem cells (USSCs) that we previously demonstrated to significantly improve wound healing and prolong the survival of col7a1\u2212\/\u2212 mice showed the ability to suppress TGF\u03b2 signaling and MMP-9 and MMP-13 expression meanwhile upregulating anti-fibrotic TGF\u03b23 and decorin. In parallel, we cocultured USSCs in a transwell with RDEB patient-derived fibroblasts, keratinocytes, and cSCC, respectively. The patient-derived cells were constitutively active for STAT, but not TGF\u03b2 signaling. Moreover, the levels of MMP-9 and MMP-13 were significantly elevated in the patient derived-keratinocytes and cSCCs. Although USSC coculture did not inhibit STAT signaling, it significantly suppressed the secretion of MMP-9 and MMP-13, and interferon (IFN)-\u03b3 from RDEB patient-derived cells. Since epithelial expression of these MMPs is a biomarker of malignant transformation and correlates with the degree of tumor invasion, these results suggest a potential role for USSCs in mitigating epithelial malignancy, in addition to their anti-inflammatory and anti-fibrotic functions.<\/jats:p>","DOI":"10.1002\/stem.2907","type":"journal-article","created":{"date-parts":[[2018,9,24]],"date-time":"2018-09-24T09:01:08Z","timestamp":1537779668000},"page":"1839-1850","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Cord Blood-Derived Stem Cells Suppress Fibrosis and May Prevent Malignant Progression in Recessive Dystrophic Epidermolysis Bullosa"],"prefix":"10.1093","volume":"36","author":[{"given":"Yanling","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Pediatrics, New York Medical College, Valhalla, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larisa","family":"Ivanova","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, New York Medical College, Valhalla, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwen","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Surgery, Tianjin Hospital, Tianjin Academy of Integrative Medicine, Tianjin, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor","family":"Plumer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, New York Medical College, Valhalla, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Hamby","sequence":"additional","affiliation":[{"name":"Department of Immunology & Microbiology, New York Medical College, Valhalla, New 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