Improvement in infected wound healing in type 1 diabetic rat by the synergistic effect of photobiomodulation therapy and conditioned medium

J Cell Biochem. 2019 Jun;120(6):9906-9916. doi: 10.1002/jcb.28273. Epub 2018 Dec 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • Culture Media, Conditioned / pharmacology
  • Diabetes Mellitus, Experimental* / metabolism
  • Diabetes Mellitus, Experimental* / microbiology
  • Diabetes Mellitus, Experimental* / pathology
  • Diabetes Mellitus, Experimental* / radiotherapy
  • Diabetes Mellitus, Type 1* / metabolism
  • Diabetes Mellitus, Type 1* / microbiology
  • Diabetes Mellitus, Type 1* / pathology
  • Diabetes Mellitus, Type 1* / radiotherapy
  • Humans
  • Low-Level Light Therapy*
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / pathology
  • Methicillin-Resistant Staphylococcus aureus / metabolism*
  • Rats
  • Staphylococcal Infections* / metabolism
  • Staphylococcal Infections* / microbiology
  • Staphylococcal Infections* / pathology
  • Staphylococcal Infections* / radiotherapy
  • Wound Healing* / drug effects
  • Wound Healing* / radiation effects
  • Wound Infection* / metabolism
  • Wound Infection* / microbiology
  • Wound Infection* / pathology
  • Wound Infection* / radiotherapy

Substances

  • Culture Media, Conditioned