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MicroRNA-155 mediates multiple gene regulations pertinent to the role of human adipose-derived mesenchymal stem cells in skin regeneration
Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Modern Sci & Arts Univ, Egypt.ORCID iD: 0000-0003-3894-6849
Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.ORCID iD: 0000-0003-4940-5538
Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences, Core Facility.ORCID iD: 0000-0002-5649-4658
Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
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2024 (English)In: Frontiers in Bioengineering and Biotechnology, E-ISSN 2296-4185, Vol. 12, article id 1328504Article in journal (Refereed) Published
Abstract [en]

Introduction: The role of Adipose-derived mesenchymal stem cells (AD-MSCs) in skin wound healing remains to be fully characterized. This study aims to evaluate the regenerative potential of autologous AD-MSCs in a non-healing porcine wound model, in addition to elucidate key miRNA-mediated epigenetic regulations that underlie the regenerative potential of AD-MSCs in wounds.Methods: The regenerative potential of autologous AD-MSCs was evaluated in porcine model using histopathology and spatial frequency domain imaging. Then, the correlations between miRNAs and proteins of AD-MSCs were evaluated using an integration analysis in primary human AD-MSCs in comparison to primary human keratinocytes. Transfection study of AD-MSCs was conducted to validate the bioinformatics data.Results: Autologous porcine AD-MSCs improved wound epithelialization and skin properties in comparison to control wounds. We identified 26 proteins upregulated in human AD-MSCs, including growth and angiogenic factors, chemokines and inflammatory cytokines. Pathway enrichment analysis highlighted cell signalling-associated pathways and immunomodulatory pathways. miRNA-target modelling revealed regulations related to genes encoding for 16 upregulated proteins. miR-155-5p was predicted to regulate Fibroblast growth factor 2 and 7, C-C motif chemokine ligand 2 and Vascular cell adhesion molecule 1. Transfecting human AD-MSCs cell line with anti-miR-155 showed transient gene silencing of the four proteins at 24 h post-transfection.Discussion: This study proposes a positive miR-155-mediated gene regulation of key factors involved in wound healing. The study represents a promising approach for miRNA-based and cell-free regenerative treatment for difficult-to-heal wounds. The therapeutic potential of miR-155 and its identified targets should be further explored in-vivo.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA , 2024. Vol. 12, article id 1328504
Keywords [en]
adipose-derived mesenchymal stem cells; miRNA; miR-155-5p; proteome; porcine wound model; wound healing; fibroblast growth factors
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:liu:diva-202262DOI: 10.3389/fbioe.2024.1328504ISI: 001194509000001PubMedID: 38562669OAI: oai:DiVA.org:liu-202262DiVA, id: diva2:1849886
Note

Funding Agencies|Centre for Advanced Medical Product, Sweden; Hand and Plastic Surgery Department, Linkoeping University Hospital, Region Ostergoetland, Sweden; Knut and Alice Wallenberg Foundation through the Wallenberg Centre for Molecular Medicine at Linkoeping University

Available from: 2024-04-09 Created: 2024-04-09 Last updated: 2024-04-09

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Shahin, HadyBelcastro, LuigiDas, JyotirmoyPerdiki Grigoriadi, MarinaSaager, RolfSteinvall, IngridSjöberg, FolkeOlofsson, PiaElmasry, MoustafaElserafy, Ahmed
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Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health SciencesDepartment of Hand and Plastic SurgeryDivision of Biomedical EngineeringFaculty of Science & EngineeringDivision of Cell BiologyCore FacilityDivision of NeurobiologyClinical pathology
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Frontiers in Bioengineering and Biotechnology
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

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