PMID- 37671699 OWN - NLM STAT- MEDLINE DCOM- 20231124 LR - 20231204 IS - 1746-076X (Electronic) IS - 1746-0751 (Linking) VI - 18 IP - 11 DP - 2023 Nov TI - Secretome profile of TNF-alpha-induced human umbilical cord mesenchymal stem cells unveils biological processes relevant to skin wound healing. PG - 839-856 LID - 10.2217/rme-2023-0085 [doi] AB - Aim: To profile and study the proteins responsible for the beneficial effect of the TNF-alpha-induced human umbilical cord mesenchymal stem cells (hUCMSCs) secretome in wound healing. Methods: The hUCMSCs secretome was generated with (induced) or without (uninduced) TNF-alpha and was subsequently analyzed by liquid chromatography-mass spectrometry, immunoassay and in vitro scratch assay. Results: 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. Conclusion: The secretome from induced hUCMSCs includes factors that promote wound closure. FAU - Tai, Lihui AU - Tai L AUID- ORCID: 0009-0007-6141-6084 AD - Cytopeutics Sdn Bhd, Suite 2-3 2nd floor, Bio-X Centre, Persiaran Cyberpoint Selatan, Cyber 8, 63000, Cyberjaya, Selangor, Malaysia. FAU - Saffery, Nik Syazana AU - Saffery NS AUID- ORCID: 0009-0002-8860-2681 AD - Cytopeutics Sdn Bhd, Suite 2-3 2nd floor, Bio-X Centre, Persiaran Cyberpoint Selatan, Cyber 8, 63000, Cyberjaya, Selangor, Malaysia. FAU - Chin, Sze Piaw AU - Chin SP AUID- ORCID: 0000-0003-2386-7435 AD - Cytopeutics Sdn Bhd, Suite 2-3 2nd floor, Bio-X Centre, Persiaran Cyberpoint Selatan, Cyber 8, 63000, Cyberjaya, Selangor, Malaysia. FAU - Cheong, Soon Keng AU - Cheong SK AUID- ORCID: 0000-0002-3507-6713 AD - Cytopeutics Sdn Bhd, Suite 2-3 2nd floor, Bio-X Centre, Persiaran Cyberpoint Selatan, Cyber 8, 63000, Cyberjaya, Selangor, Malaysia. AD - M. Kandiah Faculty of Medicine & Health Sciences (MK FMHS), Universiti Tunku Abdul Rahman Sungai Long City Campus, Jalan Sungai Long, Bandar Sungai Long, Cheras, 43000, Kajang, Selangor, Malaysia. LA - eng PT - Journal Article DEP - 20230906 PL - England TA - Regen Med JT - Regenerative medicine JID - 101278116 RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Humans MH - *Tumor Necrosis Factor-alpha/metabolism MH - Secretome MH - Proteomics MH - Wound Healing MH - *Mesenchymal Stem Cells/metabolism MH - Umbilical Cord/metabolism OAB - 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. OABL- eng OTO - NOTNLM OT - TNF-alpha OT - protein profiling OT - secretome OT - umbilical cord-derived MSCs OT - wound healing EDAT- 2023/09/06 12:42 MHDA- 2023/11/24 06:43 CRDT- 2023/09/06 06:53 PHST- 2023/11/24 06:43 [medline] PHST- 2023/09/06 12:42 [pubmed] PHST- 2023/09/06 06:53 [entrez] AID - 10.2217/rme-2023-0085 [doi] PST - ppublish SO - Regen Med. 2023 Nov;18(11):839-856. doi: 10.2217/rme-2023-0085. Epub 2023 Sep 6.