Identification of a physiologic vasculogenic fibroblast state to achieve tissue repair.

Autor: Pal D; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.; Department of Surgery, The Ohio State University, Columbus, OH, 43210, USA.; Department of Biomedical Engineering, Indian Institute of Technology Ropar, Rupnagar, Punjab, 140001, India., Ghatak S; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.; Department of Surgery, The Ohio State University, Columbus, OH, 43210, USA., Singh K; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.; Department of Surgery, The Ohio State University, Columbus, OH, 43210, USA., Abouhashem AS; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Kumar M; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., El Masry MS; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.; Department of Surgery, The Ohio State University, Columbus, OH, 43210, USA., Mohanty SK; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Palakurti R; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Rustagi Y; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Tabasum S; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Khona DK; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.; Department of Surgery, The Ohio State University, Columbus, OH, 43210, USA., Khanna S; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.; Department of Surgery, The Ohio State University, Columbus, OH, 43210, USA., Kacar S; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Srivastava R; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Bhasme P; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Verma SS; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Hernandez E; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Sharma A; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Reese D; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Verma P; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Ghosh N; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.; Department of Surgery, The Ohio State University, Columbus, OH, 43210, USA., Gorain M; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Wan J; Center for Computational Biology and Bioinformatics (CCBB), Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Liu S; Center for Computational Biology and Bioinformatics (CCBB), Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Liu Y; Center for Computational Biology and Bioinformatics (CCBB), Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Castro NH; Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA., Gnyawali SC; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.; Department of Surgery, The Ohio State University, Columbus, OH, 43210, USA., Lawrence W; Department of Surgery, The Ohio State University, Columbus, OH, 43210, USA., Moore J; Department of Surgery, The Ohio State University, Columbus, OH, 43210, USA.; Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA., Perez DG; Department of Surgery, The Ohio State University, Columbus, OH, 43210, USA.; Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA., Roy S; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.; Department of Surgery, The Ohio State University, Columbus, OH, 43210, USA., Yoder MC; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Sen CK; Indiana Center for Regenerative Medicine & Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. cksen@iu.edu.; Department of Surgery, The Ohio State University, Columbus, OH, 43210, USA. cksen@iu.edu.; Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA. cksen@iu.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Feb 28; Vol. 14 (1), pp. 1129. Date of Electronic Publication: 2023 Feb 28.
DOI: 10.1038/s41467-023-36665-z
Abstrakt: Tissue injury to skin diminishes miR-200b in dermal fibroblasts. Fibroblasts are widely reported to directly reprogram into endothelial-like cells and we hypothesized that miR-200b inhibition may cause such changes. We transfected human dermal fibroblasts with anti-miR-200b oligonucleotide, then using single cell RNA sequencing, identified emergence of a vasculogenic subset with a distinct fibroblast transcriptome and demonstrated blood vessel forming function in vivo. Anti-miR-200b delivery to murine injury sites likewise enhanced tissue perfusion, wound closure, and vasculogenic fibroblast contribution to perfused vessels in a FLI1 dependent manner. Vasculogenic fibroblast subset emergence was blunted in delayed healing wounds of diabetic animals but, topical tissue nanotransfection of a single anti-miR-200b oligonucleotide was sufficient to restore FLI1 expression, vasculogenic fibroblast emergence, tissue perfusion, and wound healing. Augmenting a physiologic tissue injury adaptive response mechanism that produces a vasculogenic fibroblast state change opens new avenues for therapeutic tissue vascularization of ischemic wounds.
(© 2023. The Author(s).)
Databáze: MEDLINE
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