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Improvement in infected wound healing in type 1 diabetic rat by the synergistic effect of photobiomodulation therapy and conditioned medium
Authors:Mohammadjavad Fridoni PhD  Reza Kouhkheil MSc  Mohammad-Amin Abdollhifar PhD  Abdollah Amini PhD  Mahdi Ghatrehsamani PhD  Seyed Kamran Ghoreishi PhD  Sufan Chien  Sahar Bayat  Mohammad Bayat PhD
Affiliation:1. Department of Anatomical Sciences, School of Medicine, Zanjan University of Medical Sciences and Price Institue Of Surgical Research, University of Louisville, Kentucky, Zanjan, Iran;2. Department of Biology and Anatomical Sciences, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran;3. Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran;4. Department of Statistics, University of Qom, Qom, Iran;5. Price Institute of Surgical Research, University of Louisville, and Noveratech LLC of Louisville, Louisville, Kentucky;6. Atherton High School, Louisville, Kentucky
Abstract:We investigated the effects of photobiomodulation therapy (PBMT) and conditioned medium (CM) of human bone marrow mesenchymal stem cells (hBM-MSC) individually and/or in combination on the stereological parameters and the expression of basic fibroblast growth factor (bFGF), hypoxia-inducible factor (HIF-1α), and stromal cell–derived factor-1α (SDF-1α) in a wound model infected with methicillin-resistant Staphylococcus aureus (MRSA) in diabetic rats. CM was provided by culturing hBM-MSCs. Type 1 diabetes mellitus (T1DM) was induced in 72 rats, divided into four groups, harboring 18 rats each: group 1 served as a control group, group 2 received PBMT, group 3 received CM, and group 4 received CM + PBMT. On days 4, 7, and 15, six animals from each group were euthanized and the skin samples were separated for stereology examination and gene expression analysis by real-time polymerase chain reaction. In the CM + PBMT, CM, and PBMT groups, significant decreases were induced in the number of neutrophils (1460 ± 93, 1854 ± 138, 1719 ± 248) and macrophages (539 ± 69, 804 ± 63, 912 ± 41), and significant increases in the number of fibroblasts (1073 ± 116, 836 ± 75, 912 ± 41) and angiogenesis (15 230 ± 516, 13 318 ± 1116, 14 041 ± 867), compared with those of the control group (2690 ± 371, 1139 ± 145, 566 ± 90, 12 585 ± 1219). Interestingly, the findings of the stereological examination in the CM + PBMT group were statistically more significant than those in the other groups. In the PBMT group, in most cases, the expression of bFGF, HIF-1α, and SDF-1α, on day 4 (27.7 ± 0.14, 28.8 ± 0.52, 27.5 ± 0.54) and day 7 (26.8 ± 1.4, 29.6 ± 1.4, 28.3 ± 1.2) were more significant than those in the control (day 4, 19.3 ± 0.42, 25.5 ± 0.08, 22.6 ± 0.04; day 7, 22.3 ± 0.22, 28.3 ± 0.59, 24.3 ± 0.19) and other treatment groups. The application of PBMT + CM induced anti-inflammatory and angiogenic activities, and hastened wound healing process in a T1 DM model of MRSA infected wound.
Keywords:diabetes mellitus  diabetic foot ulcer  human bone marrow mesenchymal stem cell-conditioned medium  low-level laser therapy  methicillin-resistant staphylococcal aureus  phobiomodulation therapy  rat  real-time PCR  stereology
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