Secretome profile of TNF-α-induced human umbilical cord mesenchymal stem cells unveils biological processes relevant to skin wound healing

• Published in: Regenerative medicine 2023-11, Vol.18 (11), p.839-856
• Main Authors: Tai, Lihui, Saffery, Nik Syazana, Chin, Sze Piaw, Cheong, Soon Keng
• Format: Article
• Language: English
• Subjects: protein profiling; secretome; TNF-α; umbilical cord-derived MSCs; wound healing
• ISSN: 1746-0751; 1746-076X
• DOI: 10.2217/rme-2023-0085

To profile and study the proteins responsible for the beneficial effect of the TNF-α-induced human umbilical cord mesenchymal stem cells (hUCMSCs) secretome in wound healing. The hUCMSCs secretome was generated with (induced) or without (uninduced) TNF-α and was subsequently analyzed by liquid chromatography–mass spectrometry, immunoassay and scratch assay. Proteomic analysis revealed approximately 260 proteins, including 51 and 55 unique proteins in the induced and uninduced secretomes, respectively. Gene ontology analysis disclosed that differential proteins in the induced secretome mainly involved inflammation-related terms. The induced secretome, consisting of higher levels of FGFb, VEGF, PDGF and IL-6, significantly accelerated wound closure and enhanced MMP-13 secretion in HaCaT keratinocytes. The secretome from induced hUCMSCs includes factors that promote wound closure. An interference or delay in normal stages of the wound healing process, particularly in the elderly population and individuals with comorbid conditions, generally results in the development of chronic wounds with uncontrolled inflammation. Innovative therapies, such as stem cells and their secreted factors (the ‘secretome’) are potential tools in regulating wound repair. We used an inflammatory factor to precondition human umbilical cord stem cells to generate a secretome (induced secretome) that was beneficial in response to the inflammation environment. Approximately 260 proteins were detected. Further analysis identified that unique proteins in the induced secretome are mainly related to inflammation-related biological processes. We also demonstrated that the induced secretome enhanced the wound closure rate in human keratinocyte cells, as compared with the control and naive secretome. This is likely due to the higher levels of growth factors and cytokines in the induced secretome, which play significant roles in the regulation of the wound healing process. The present findings provide useful information to better understand the role of the human umbilical cord mesenchymal stem cell secretome, especially in an inflammatory niche, as well as the proteins that are important for clinical translation in wound repair.