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Publication : Direct conversion of injury-site myeloid cells to fibroblast-like cells of granulation tissue.

First Author  Sinha M Year  2018
Journal  Nat Commun Volume  9
Issue  1 Pages  936
PubMed ID  29507336 Mgi Jnum  J:265510
Mgi Id  MGI:6149259 Doi  10.1038/s41467-018-03208-w
Citation  Sinha M, et al. (2018) Direct conversion of injury-site myeloid cells to fibroblast-like cells of granulation tissue. Nat Commun 9(1):936
abstractText  Inflammation, following injury, induces cellular plasticity as an inherent component of physiological tissue repair. The dominant fate of wound macrophages is unclear and debated. Here we show that two-thirds of all granulation tissue fibroblasts, otherwise known to be of mesenchymal origin, are derived from myeloid cells which are likely to be wound macrophages. Conversion of myeloid to fibroblast-like cells is impaired in diabetic wounds. In cross-talk between keratinocytes and myeloid cells, miR-21 packaged in extracellular vesicles (EV) is required for cell conversion. EV from wound fluid of healing chronic wound patients is rich in miR-21 and causes cell conversion more effectively compared to that by fluid from non-healing patients. Impaired conversion in diabetic wound tissue is rescued by targeted nanoparticle-based delivery of miR-21 to macrophages. This work introduces a paradigm wherein myeloid cells are recognized as a major source of fibroblast-like cells in the granulation tissue.
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