MMP9 secreted from mononuclear cell quality and quantity culture mediates STAT3 phosphorylation and fibroblast migration in wounds
| Autor: | Hiroko Hagiwara, Rica Tanaka, Makiko Kado, Tsubame Nishikai-Yan Shen, Satoshi Fujimura, Hiroshi Mizuno |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
HRP
Horseradish peroxidase Medicine (General) Angiogenesis VEGF Vascular endothelial growth factor Biomedical Engineering Wound healing MMP Matrix metallopeptidase SE Standard error Cell therapy Fibroblast migration Biomaterials Dermal fibroblast R5-920 QQc Quality and quantity culture medicine Fibroblast BM Bone marrow DMEM Dulbecco's modified Eagle's medium MNC Monocyte cell PBMNC Peripheral blood monocyte cells QH573-671 Chemistry MMP9 EPC Endothelial progenitor cells PB Peripheral blood BMMNC Bone marrow mononuclear cells PBS Phosphate-buffered saline Cell biology Intracellular signal transduction medicine.anatomical_structure Cell culture FBS Fetal bovine serum Original Article Cytology MNC-QQc Developmental Biology |
| Zdroj: | Regenerative Therapy, Vol 18, Iss, Pp 464-471 (2021) Regenerative Therapy |
| ISSN: | 2352-3204 |
| Popis: | Introduction Intractable ulcers may ultimately lead to amputation. To promote wound healing, researchers developed a serum-free ex vivo peripheral blood mononuclear cell quality and quantity culture (MNC-QQc) as a source for cell therapy. In mice, pigs, and even humans, cell therapy with MNC-QQc reportedly yields a high regenerative efficacy. However, the mechanism of wound healing by MNC-QQc cells remains largely unknown. Hence, using an in vitro wound healing model, this study aimed to investigate MNC-QQc cells and the migratory potential of dermal fibroblasts. Methods After separation from a 50 mL blood sample from healthy individuals, mononuclear cells were cultured for 7 days in a serum-free ex vivo expansion system with five different cytokines (MNC-QQc method). The effects of MNC-QQc cells on human dermal fibroblast migration were observed by scratch assay. An angiogenesis array screened the MNC-QQc cell supernatant for proteins related to wound healing. Finally, fibroblast migration was confirmed by observing the intracellular signal transduction pathways via Western blot. Results The migration of fibroblasts co-cultured with MNC-QQc cells increased by matrix metallopeptidase-9 (MMP9) secretion, as suggested by the angiogenesis array. Furthermore, the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in fibroblast/MNC-QQc cell co-culture and fibroblast culture with added recombinant human MMP9 protein increased. When fibroblasts were cultured with either an MMP9 inhibitor or a STAT3 inhibitor, both fibroblast migration and STAT3 phosphorylation were significantly suppressed. Conclusions MNC-QQc cells promote wound healing by the secretion of MMP9, which induces fibroblast migration via the STAT3 signaling pathway. |
| Databáze: | OpenAIRE |
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