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A unique subset of MSCs expressing ATP-binding cassette subfamily member 5 (ABCB5) resides in the reticular dermis and exhibits similar immunomodulatory characteristics to BM-MSCs. Our work aimed to test the hypothesis that skin-derived ABCB5+ dermal MSCs (DSCs) possess superior skin homing ability compared to BM-MSCs in immunodeficient NOD-scid IL2rgammanull (NSG) mice. Compared to BM-MSCs, peripherally injected ABCB5+ DSCs demonstrated superior homing and engraftment of wounds. Furthermore, ABCB5+ DSCs vs BM-MSCs cocultured with macrophages induced less anti-inflammatory interleukin-1 receptor antagonist (IL-1RA) production. RNA sequencing of ABCB5+ DSCs compared to BM-MSCs showed unique expression of major histocompatibility complex class II and Homeobox (Hox) genes, specifically HOXA3. Critical to inducing migration of endothelial and epithelial cells for wound repair, increased expression of HOXA3 may explain superior skin homing properties of ABCB5+ DSCs. Further discernment of the immunomodulatory mechanisms among MSC populations could have broader regenerative medicine implications beyond RDEB treatment.<\/jats:p>","DOI":"10.1002\/stem.3356","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T15:03:42Z","timestamp":1630940622000},"page":"897-903","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["ABCB5+ Dermal Mesenchymal Stromal Cells with Favorable Skin Homing and Local Immunomodulation for Recessive Dystrophic Epidermolysis Bullosa Treatment"],"prefix":"10.1093","volume":"39","author":[{"given":"Julia","family":"Riedl","sequence":"first","affiliation":[{"name":"Medical Scientist Training Program (MD\/PhD) \u00a0University of Minnesota, Minneapolis, Minnesota, USA"},{"name":"Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Ganss","sequence":"additional","affiliation":[{"name":"TICEBA GmbH, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha Y.","family":"Frank","sequence":"additional","affiliation":[{"name":"Department of Medicine \u00a0VA Boston Healthcare System, Boston, Massachusetts, USA"},{"name":"Division of Genetics \u00a0Brigham and Women's Hospital, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1312-0488","authenticated-orcid":false,"given":"Markus H.","family":"Frank","sequence":"additional","affiliation":[{"name":"Transplant Research Program \u00a0Boston Children's Hospital, Boston, Massachusetts, USA"},{"name":"School of Medical and Health Sciences \u00a0Edith Cowan University, Perth, Western Australia, 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