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Photobiomodulation, alone or combined with adipose-derived stem cells, reduces inflammation by modulation of microRNA-146a and interleukin-1ß in a delayed-healing infected wound in diabetic rats

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Abstract

Diabetic wounds are categorized by chronic inflammation, leading to the development of diabetic foot ulcers, which cause amputation and death. Herewith, we examined the effect of photobiomodulation (PBM) plus allogeneic diabetic adipose tissue-derived stem cells (ad-ADS) on stereological parameters and expression levels of interleukin (IL)-1ß and microRNA (miRNA)-146a in the inflammatory (day 4) and proliferation (day 8) stages of wound healing in an ischemic infected (with 2×107 colony-forming units of methicillin-resistant Staphylococcus aureus) delayed healing wound model (IIDHWM) in type I diabetic (TIDM) rats. There were five groups of rats: group 1 control (C); group 2 (CELL) in which rat wounds received 1×106 ad-ADS; group 3 (CL) in which rat wounds received the ad-ADS and were subsequently exposed to PBM(890 nm, 80 Hz, 3.5 J/cm2, in vivo); group 4 (CP) in which the ad-ADS preconditioned by the PBM(630 nm + 810 nm, 0.05 W, 1.2 J/cm2, 3 times) were implanted into rat wounds; group 5 (CLP) in which the PBM preconditioned ad-ADS were implanted into rat wounds, which were then exposed to PBM. On both days, significantly better histological results were seen in all experimental groups except control. Significantly better histological results were observed in the ad-ADS plus PBM treatment correlated to the ad-ADS alone group (p<0.05). Overall, PBM preconditioned ad-ADS followed by PBM of the wound showed the most significant improvement in histological measures correlated to the other experimental groups (p<0.05). On days 4 and 8, IL-1 β levels of all experimental groups were lower than the control group; however, on day 8, only the CLP group was different (p<0.01). On day 4, miR-146a expression levels were substantially greater in the CLP and CELL groups correlated to the other groups, on day 8 miR-146a in all treatment groups was upper than C (p<0.01). ad-ADS plus PBM, ad-ADS, and PBM all improved the inflammatory phase of wound healing in an IIDHWM in TIDM1 rats by reducing inflammatory cells (neutrophils, macrophages) and IL-1ß, and increasing miRNA-146a. The ad-ADS+PBM combination was better than either ad-ADS or PBM alone, because of the higher proliferative and anti-inflammatory effects of the PBM+ad-ADS regimen.

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Acknowledgements

The present article is financially supported by “Research Department of the School of Medicine at Shahid Beheshti University of Medical Sciences, Tehran, Iran” (grant no. 25918), and this article has been extracted from the thesis written by Ms. Fahimeh Ghasemi Moravej (IR.SBMU.MSP.REC.1400.570). MRH was supported by US NIH Grants R01AI050875 and R21AI121700. Authors acknowledge Soroush Bayat for revising Fig. 1.

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Authors and Affiliations

  1. Department of Biology and Anatomical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Fahimeh Ghasemi Moravej, Abdollah Amini, Reza Masteri Farahani, Houssein Ahmadi, Hamidreza Omidi & Mohammad Bayat

  2. Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Samira Mohammadi-Yeganeh

  3. Department of Anatomical Sciences & Cognitive Neuroscience, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Atarodalsadat Mostafavinia

  4. College of Pharmacy, University of Kentucky, 789 South Limestone, Lexington, KY, 40536, USA

    Fatemehalsadat Rezaei

  5. Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Latif Gachkar

  6. Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, South Africa, and Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran

    Michael R Hamblin

  7. Price Institute of Surgical Research, University of Louisville, and Noveratech LLC, Louisville, KY, USA

    Sufan Chien & Mohammad Bayat

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  1. Fahimeh Ghasemi Moravej
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Contributions

FGM, HA, HO, and FR performed the experiments. AA and AM performed the statistical tests. SC added comments. MB designed the project and drafted the paper. MRH critically edited the paper for content and meaning.

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Correspondence to Abdollah Amini or Mohammad Bayat.

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Competing interests

Michael R Hamblin declares the following potential conflicts of interest. Scientific Advisory Boards: Transdermal Cap Inc, Cleveland, OH; Hologenix Inc. Santa Monica, CA; Vielight, Toronto, Canada; JOOVV Inc, Minneapolis-St. Paul MN; Sunlighten, Kansas City, MO; Consulting; USHIO Corp, Japan; Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany; Klox Asia, Guangzhou, China. Stockholding: Niraxx Light Therapeutics, Inc, Irvine CA; JelikaLite Corp, New York NY. The other authors report they have no conflicts of interest.

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Moravej, F.G., Amini, A., Masteri Farahani, R. et al. Photobiomodulation, alone or combined with adipose-derived stem cells, reduces inflammation by modulation of microRNA-146a and interleukin-1ß in a delayed-healing infected wound in diabetic rats. Lasers Med Sci 38, 129 (2023). https://doi.org/10.1007/s10103-023-03786-2

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