Supplementary Material for: Mesenchymal stromal cell-secretome for therapeutic application in skin wound healing: a systematic review of preclinical studies

Non-healing skin wounds remain a challenge in the healthcare system. In this sense, it is suggested that the secretome of mesenchymal stromal cells (MSCs) can be effective as a therapeutic strategy for regenerative medicine. Therefore, this systematic review aimed to determine the effects of treatment with secretome derived from MSCs on the healing of skin wounds in preclinical model of rodents (mice and rats). Studies were systematically retrieved from six databases and grey literature that provided 1172 records, of which 25 met the inclusion criteria for qualitative analysis. Results revealed substantial heterogeneity among studies concerning experimental designs and methodologies, resulting in a high risk of bias. Together, the selected studies reported that treatment improved wound healing by (I) accelerating wound closure and improving skin repair quality; (II) reducing inflammation by decreasing the number of cells and inflammatory cytokines, accompanied by polarization of the M2 macrophage; (III) complete re-epithelialization and epidermal reorganization; (IV) neovascularization promoted by proliferation of endothelial cells (CD34+) and increased levels of pro-angiogenic mediators; (V) better scar quality promoted by increased expression of collagen types I and III, as well as improved deposition and remodeling of collagen fibers. In conclusion, despite the need for alignment of methodological protocols and transparent reports in future studies, results show that the secretome of MSCs from different tissue sources corresponds to a promising tool of regenerative medicine for the treatment of skin wounds.