PMID- 34366213 OWN - NLM STAT- MEDLINE DCOM- 20211210 LR - 20211214 IS - 0965-206X (Print) IS - 0965-206X (Linking) VI - 30 IP - 4 DP - 2021 Nov TI - SA/G hydrogel containing NRF2-engineered HEK-293-derived CM improves wound healing efficacy of WJ-MSCs in a rat model of excision injury. PG - 527-536 LID - S0965-206X(21)00094-2 [pii] LID - 10.1016/j.jtv.2021.07.009 [doi] AB - AIM OF THE STUDY: Skin wounds are a major public health issue due to the lack of real effective remedies. Mesenchymal stem cells (MSCs) are considered as a promising therapeutic strategy for wound injuries; however, low survival rate following transplantation limited their application. In an attempt to introduce a novel potential wound dressing and improve wound healing properties, the current study was conducted. MATERIAL AND METHODS: we prepared conditioned medium (CM) harvested from HEK-293 cells overexpressing nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of antioxidant genes expression. Then, the CM was loaded in a biodegradable hydrogel. Next, in an animal model of full-thickness excision wound, wharton's jelly derived-mesenchymal stem cells (WJ-MSCs) were transplanted at the margins of the wound followed by application of the hydrogel on injury site. Finally, wound healing characteristics were evaluated by proper methods. RESULTS: Our findings revealed that, the NRF2-CM protected the WJ-MSCs against H(2)O(2)-induced toxicity in vitro. Furthermore, in vivo results showed that, SA/G hydrogel containing NRF2-CM significantly (P < 0.01) promoted WJ-MSCs survival, increased angiogenesis, accelerated wound contraction, and promoted wound healing compared to other groups. CONCLUSION: Though further preclinical and clinical studies regarding mechanisms behind the protection and also safety of the strategy are needed, our findings strongly suggest that the prepared wound dressing enhanced the efficacy of therapeutic potential of WJ-MSCs by providing an enriched/antioxidant niche support. CI - Copyright (c) 2021 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved. FAU - Sabzevari, Reza AU - Sabzevari R AD - Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran. FAU - Mohammadi Roushandeh, Amaneh AU - Mohammadi Roushandeh A AD - Burn and Regenerative Medicine Research Center, Medicine Faculty, Guilan University of Medical Sciences, Rasht, Iran. FAU - Alijani-Ghazyani, Zahra AU - Alijani-Ghazyani Z AD - Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran. FAU - Jahanian-Najafabadi, Ali AU - Jahanian-Najafabadi A AD - Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, IR Iran. FAU - Habibi Roudkenar, Mehryar AU - Habibi Roudkenar M AD - Burn and Regenerative Medicine Research Center, Medicine Faculty, Guilan University of Medical Sciences, Rasht, Iran. Electronic address: roudkenar@gums.ac.ir. LA - eng PT - Journal Article DEP - 20210804 PL - England TA - J Tissue Viability JT - Journal of tissue viability JID - 9306822 RN - 0 (Culture Media, Conditioned) RN - 0 (Hydrogels) RN - 0 (NF-E2-Related Factor 2) RN - BBX060AN9V (Hydrogen Peroxide) MH - Animals MH - Culture Media, Conditioned MH - HEK293 Cells MH - Humans MH - Hydrogels MH - Hydrogen Peroxide MH - *Mesenchymal Stem Cell Transplantation MH - *Mesenchymal Stem Cells MH - NF-E2-Related Factor 2 MH - Rats MH - Wound Healing OTO - NOTNLM OT - Conditioned medium OT - Hydrogel OT - NRF2 OT - WJ-MSCs OT - Wound healing EDAT- 2021/08/10 06:00 MHDA- 2021/12/15 06:00 CRDT- 2021/08/09 05:40 PHST- 2021/01/14 00:00 [received] PHST- 2021/05/03 00:00 [revised] PHST- 2021/07/28 00:00 [accepted] PHST- 2021/08/10 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/08/09 05:40 [entrez] AID - S0965-206X(21)00094-2 [pii] AID - 10.1016/j.jtv.2021.07.009 [doi] PST - ppublish SO - J Tissue Viability. 2021 Nov;30(4):527-536. doi: 10.1016/j.jtv.2021.07.009. Epub 2021 Aug 4.