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Mesenchymal stem cells (MSCs) found within the HCT graft are believed to be partially responsible for this amelioration, in part due to their intrinsic immunomodulatory and trophic properties and also because they have been shown to restore C7 protein following intradermal injections in models of RDEB. However, MSCs have not yet been demonstrated to improve disease severity as a stand-alone systemic infusion therapy. Improving the efficacy and functional utility of MSCs via a pre-transplant conditioning regimen may bring systemic MSC infusions closer to clinical practice.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>MSCs were isolated from 2- to 4-week-old mice and treated with varying concentrations of transforming growth factor-\u03b2 (TGF\u03b2; 5-20 ng\/mL), tumor necrosis factor- \u03b1 (TNF\u03b1; 10-40 ng\/mL), and stromal cell-derived factor 1-\u03b1 (SDF-1\u03b1; 30 ng\/mL) for 24-72 hours.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>We demonstrate that treating murine MSCs with exogenous TGF\u03b2 (15 ng\/mL) and TNF\u03b1 (30 ng\/mL) for 48 hours induces an 8-fold increase in <jats:italic>Col7a1<\/jats:italic> expression and a significant increase in secretion of C7 protein, and that the effects of these cytokines are both time and concentration dependent. This cytokine treatment also promotes a 4-fold increase in <jats:italic>Tsg-6<\/jats:italic> expression, a gene whose product is associated with improved wound-healing and immunosuppressive features. Finally, the addition of exogenous SDF-1\u03b1 to this regimen induces a simultaneous upregulation of <jats:italic>Col7a1, Tsg-6<\/jats:italic>, and <jats:italic>Cxcr4<\/jats:italic> expression.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>These data suggest that preconditioning represents a feasible method for improving the functional utility of MSCs in the context of RDEB stem cell transplantation, and also highlight the applicability of preconditioning principles toward other cell-based therapies aimed at treating RDEB patients.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/scrt511","type":"journal-article","created":{"date-parts":[[2014,11,6]],"date-time":"2014-11-06T12:02:19Z","timestamp":1415275339000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Preconditioning of mesenchymal stem cells for improved transplantation efficacy in recessive dystrophic epidermolysis bullosa"],"prefix":"10.1186","volume":"5","author":[{"given":"Christopher","family":"Perdoni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A","family":"McGrath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Tolar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,11,6]]},"reference":[{"key":"433_CR1","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1016\/j.jaad.2014.01.903","volume":"70","author":"JD Fine","year":"2014","unstructured":"Fine JD, Bruckner-Tuderman L, Eady RA, Bauer EA, Bauer JW, Has C, Heagerty A, Hintner H, Hovnanian A, Jonkman MF, Leigh I, Marinkovich MP, Martinez AE, McGrath JA, Mellerio JE, Moss C, Murrell DF, Shimizu H, Uitto J, Woodley D, Zambruno G: Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. 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