Skip to main content

Effect of photobiomodulation on cellular migration and survival in diabetic and hypoxic diabetic wounded fibroblast cells

Lasers in Medical Science volume 36, pages 365–374 (2021)Cite this article

Abstract

A disrupted wound repair process often leads to the development of chronic wounds, and pose a major physical, social and economic inconvenience on patients and the public health sector. Chronic wounds are a common complication seen in diabetes mellitus (DM), and often the severity necessitates amputation of the lower limbs. Recently, there has been increasing evidence that photobiomodulation (PBM) initiates wound healing, including increased protein transcription for cell proliferation, viability, migration and tissue reepithelialisation. Here, the hypothesis that PBM at a wavelength of 660 nm and energy density of 5 J/cm2 regulates wound repair in diabetic wounded and hypoxic diabetic wounded fibroblasts by enhancing cell migration and survival was investigated. PBM increased migration and survival in diabetic wounded and hypoxic diabetic wounded fibroblasts. Our findings suggest that PBM enhances migration and survival in diabetic wounded and hypoxic diabetic wounded fibroblasts, indicating that this therapeutic method may be beneficial against chronic wounds in diabetic patients.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  1. Rosińczuk J, Taradaj J, Dymarek R, Sopel M (2016) Mechanoregulation of wound healing and skin homeostasis. Biomed Res Int 3943481:1–13. https://doi.org/10.1155/2016/3943481

    Article  CAS  Google Scholar 

  2. Tracy LE, Minasian RA, Caterson EJ (2016) Extracellular matrix and dermal fibroblast function in the healing wound. Adv Wound Care 5:119–136. https://doi.org/10.1089/wound.2014.0561

    Article  Google Scholar 

  3. Rashidi S, Yadollahpour A, Mirzaiyan M (2015) Low level laser therapy for the treatment of chronic wound: clinical considerations. Biomed Pharmacol J 8:1121–1127

    Article  Google Scholar 

  4. Järbrink K, Ni G, Sönnergren H et al (2017) The humanistic and economic burden of chronic wounds: a protocol for a systematic review. Syst Rev 6:15. https://doi.org/10.1186/s13643-016-0400-8

    Article  PubMed  PubMed Central  Google Scholar 

  5. Senoo M (2013) Epidermal stem cells in homeostasis and wound repair of the skin. Adv Wound Care 2:273–282. https://doi.org/10.1089/wound.2012.0372

    Article  Google Scholar 

  6. Mariam TG, Alemayehu A, Tesfaye E et al (2017) Prevalence of diabetic foot ulcer and associated factors among adult diabetic patients who attend the diabetic follow-up Clinic at the University of Gondar Referral Hospital, North West Ethiopia, 2016: institutional-based cross-sectional study. J Diabetes Res 2017:2879249. https://doi.org/10.1155/2017/2879249

    Article  PubMed  PubMed Central  Google Scholar 

  7. Yang RH, Qi SH, Shu B et al (2016) Epidermal stem cells (ESCs) accelerate diabetic wound healing via the notch signalling pathway. Biosci Rep 36:e00364. https://doi.org/10.1042/BSR20160034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Qing C (2017) The molecular biology in wound healing & non-healing wound. Chin J Traumatol 20:189–193

    Article  Google Scholar 

  9. Castilla DM, Liu ZJ, Velazquez OC (2012) Oxygen: implications for wound healing. Adv Wound Care 6:225–230

    Article  Google Scholar 

  10. Kajagar BM, Godhi AS, Pandit A, Khatri S (2012) Efficacy of low level laser therapy on wound healing in patients with chronic diabetic foot ulcers-a randomised control trial. Indian J Surg 74:359–363

    Article  Google Scholar 

  11. Hawkins D, Houreld N, Abrahamse H (2005) Low level laser therapy (LLLT) as an effective therapeutic modality for delayed wound healing. Ann N Y Acad Sci 1056:486–493

    Article  CAS  Google Scholar 

  12. Kushibiki T, Ishihara M (2017) Biological function of low reactive level laser therapy (LLLT). Photomedicine - Advances in Clinical Practice. IntechOpen, Yohei Tanaka. Available from: https://www.intechopen.com/books/photomedicine-advances-in-clinical-practice/biological-function-of-low-reactive-level-laser-therapy-lllt-. Accessed 16.04.2019

  13. Wang X, Tian F, Soni SS, Gonzalez-Lima F, Liu H (2016) Interplay between up-regulation of cytochrome-c-oxidase and hemoglobin oxygenation induced by near-infrared laser. Sci Rep 6:30540. https://doi.org/10.1038/srep30540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hamblin MR (2017) Mechanisms and applications of the anti-inflammatory effects of photobiomodulation. AIMS Biophys 4(3):337–361

    Article  CAS  Google Scholar 

  15. De Fritas LF, Hamblin MR (2016) Proposed mechanisms of photobiomodulation or low-level light therapy. IEEE J Sel Top Quantum Electron 22:7000417. https://doi.org/10.1109/JSTQE.2016.2561201

    Article  CAS  Google Scholar 

  16. Arany PR (2008) Photobiomodulation by low power laser irradiation involves activation of latent TGF-β1. Proceedings of light-activated tissue regeneration and therapy conference. Lecture Notes in Electrical Engineering 12:207–212. https://doi.org/10.1007/978-0-387-71809-5_19

  17. Liang CC, Park AY, Guan JL (2007) In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc 2:329–333

    Article  CAS  Google Scholar 

  18. Cappiello F, Casciaro B, Mangoni ML (2018) A novel in vitro wound healing assay to evaluate cell migration. J Vis Exp 17:133. https://doi.org/10.3791/56825

    Article  CAS  Google Scholar 

  19. Hawkins D, Abrahamse H (2006) The role of laser fluence in cellviability, proliferation and membrane integrity of wounded human skin fibroblasts following helium-neon laser irradiation. Lasers Surg Med 38:74–83

    Article  Google Scholar 

  20. Houreld NN, Abrahamse H (2008) Laser light influences cellular viability and proliferation in diabetic-wounded fibroblast cells in a dose- and wavelength-dependent manner. Lasers Med Sci 23:11–18. https://doi.org/10.1007/s10103-007-0445-y

    Article  CAS  PubMed  Google Scholar 

  21. Catrina SB, Zheng X (2016) Disturbed hypoxic responses as a pathogenic mechanism of diabetic foot ulcers. Diabetes Metab Res Rev 1:179–185. https://doi.org/10.1002/dmrr.2742

    Article  CAS  Google Scholar 

  22. Nemeth AJ (1993) Lasers in wound healing. Dermat Clin 11:783–789

    Article  CAS  Google Scholar 

  23. Ayuk SM, Houreld NN, Abrahamse H (2016) The role of phobiomodulation on gene expression of cell adhesion molecules in diabetic wounded fibroblasts in vitro. J Photochem Photobiol 161:368–374

    Article  CAS  Google Scholar 

  24. Wang W, Reddy DD, Nalawade SS, Pal S, Gonzalez-Lima F, Liu H (2017) Impact of heat on metabolic and haemodynamic changes in transcranial infrared laser stimulation measured by broadband near-infrared spectroscopy. Neurophoton. 5:011004. https://doi.org/10.1117/1.NPh.5.1.011004

    Article  Google Scholar 

  25. Yu ACH, Lau AMF, Fu AWY et al (2002) Changes in ATP and ADP in cultured astrocytes under and after in vitro ischemia. Neurochem Res 27:1663–1668

    Article  CAS  Google Scholar 

  26. Jere SW, Houreld NN, Abrahamse H (2018) Photobiomodulation at 660 nm stimulates proliferation and migration of diabetic wounded cells via the expression of epidermal growth factor and the JAK/STAT pathway. J Photochem Photobiol 179:74–83

    Article  CAS  Google Scholar 

  27. Felice F, Zambito Y, Belardinelli E et al (2015) Effect of different chitosan derivatives on in vitro scratch wound assay: a comparative study. Int J Biol Macromol 76:236–241

    Article  CAS  Google Scholar 

  28. Hamdan S, Pastar I, Drakulich S et al (2017) Nanotechnology-driven therapeutic interventions in wound healing: potential uses and applications. ACS Cent Sci 3:163–175. https://doi.org/10.1021/acscentsci.6b00371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Denu RA, Nemcek S, Bloom DD et al (2016) Fibroblasts and mesenchymal stromal/stem cells are phenotypically indistinguishable. Acta Haematol 136:85–97

    Article  CAS  Google Scholar 

  30. Monsuur HN, Boink MA, Weijers EM et al (2016) Methods to study differences in cell mobility during skin wound healing in vitro. J Biomech 49:1381–1387

    Article  Google Scholar 

  31. Darby IA, Laverdet B, Bonté F, Desmoulière A (2014) Fibroblasts and myofibroblasts in wound healing. Clin Cosmet Investig Dermatol 7:301–311. https://doi.org/10.2147/CCID.S50046

    Article  PubMed  PubMed Central  Google Scholar 

  32. Nilforoushzadeh MA, Ahmadi Ashtiani HR, Jaffary F et al (2017) Dermal fibroblast cells: biology and function in skin regeneration. J Skin Stem Cell 4:e69080. https://doi.org/10.5812/jssc.69080

    Article  Google Scholar 

  33. Hodges MM, Zgheib C, Xu J, Liechty KW (2016) The role of MicroRNAs in impaired diabetic wound healing. Open access peer-reviewed chapter. Wound Healing - New insights into Ancient Challenges. Wound Healing - New insights into Ancient Challenges. https://doi.org/10.5772/63637

  34. Zhao R, Liang H, Clarke E, Jackson C, Xue M (2016) Inflammation in chronic wounds. Int J Mol 17:2085. https://doi.org/10.3390/ijms17122085

    Article  CAS  Google Scholar 

  35. Des Jardins-Park HE, Foster DS, Longaker MT (2018) Fibroblasts and wound healing: an update. Regen Med 13:491–495

    Article  CAS  Google Scholar 

  36. Frykberg RG, Banks J (2015) Challenges in the treatment of chronic wounds. Adv Wound Care 4:560–582

    Article  Google Scholar 

  37. Beckmann KH, Meyer-Hamme G, Schröder S (2014) Low level laser therapy for the treatment of diabetic foot ulcers: a critical survey. Evid Based Complement Alternat Med:626127. https://doi.org/10.1155/2014/626127

  38. Ma H, Yang JP, Tan RK, Lee HW, Han SK (2018) Effect of low-level laser therapy on proliferation and collagen synthesis of human fibroblasts in vitro. J Wound Manag Res 14:1–6. https://doi.org/10.22467/jwmr.2018.00283

    Article  Google Scholar 

  39. Shingyochi Y, Kanazawa S, Tajima S, Tanaka R, Mizuno H, Tobita MA (2017) Low-level carbon dioxide laser promotes fibroblast proliferation and migration through activation of Akt, ERK, and JNK. PLoS One 12:e0168937. https://doi.org/10.1371/journal.pone.0168937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Basso FG, Pansani TN, Turrioni AP et al (2012) In vitro wound healing improvement by low-level laser therapy application in cultured gingival fibroblasts. Int J Dent:719452. https://doi.org/10.1155/2012/719452

  41. Katz J, Bhattacharyya I, Farkhondeh-Kish F, Perez FM, Caudle RM, Heft MW (2005) Expression of the receptor of advanced glycation end products in gingival tissues of type 2 diabetes patients with chronic periodontal disease: a study utilizing immunohistochemistry and RT-PCR. J Clin Periodontol 32:40–44

    Article  CAS  Google Scholar 

  42. Mogford JE, Tawil N, Chen A, Gies D, Xia Y, Mustoe TA (2002) Effect of age and hypoxia on TGFbeta1 receptor expression and signal transduction in human dermal fibroblasts: impact on cell migration. J Cell Physiol 190:259–265

    Article  CAS  Google Scholar 

  43. Lerman OZ, Galiano RD, Armour M, Levine JP, Gurtner GC (2003) Cellular dysfunction in the diabetic fibroblast impairment in migration, vascular endothelial growth factor production, and response to hypoxia. Am J Pathol 162:303–312

    Article  CAS  Google Scholar 

  44. Li B, Wang JH (2011) Fibroblasts and myofibroblasts in wound healing: force generation and measurement. J Tissue Viability 20:108–120

    Article  Google Scholar 

  45. Douglas S, Steinbrech MD, Michael T et al (1999) Fibroblast response to hypoxia: the relationship between angiogenesis and matrix regulation. J Surg Res 84:127–133

    Article  Google Scholar 

  46. Chu YH, Chen SY, Hsieh YL, Teng YH, Cheng YJ (2018) Low-level laser therapy prevents endothelial cells from TNF-α/cycloheximide-induced apoptosis. Lasers Med Sci 33:279–286

    Article  Google Scholar 

  47. Pansani TN, Basso FG, Turirioni AP, Kurachi C, Hebling J, de Souza Costa CA (2014) Effects of low-level laser therapy on the proliferation and apoptosis of gingival fibroblasts treated with zoledronic acid. Int J Oral Maxillofac Surg 43:1030–1034

    Article  Google Scholar 

Download references

Funding

This work was supported by the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa (Grant No 98337), as well as grants received from the University of Johannesburg (URC), the African Laser Centre (ALC), the National Research Foundation (NRF) and the Council for Scientific and Industrial Research (CSIR)-National Laser Centre (NLC) Laser Rental Pool Program.

Author information

Authors and Affiliations

  1. Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein, 2028, South Africa

    Sandy W. Jere, Nicolette N. Houreld & Heidi Abrahamse

Authors
  1. Sandy W. Jere
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nicolette N. Houreld
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Heidi Abrahamse
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization, S.W.J. performed the experiments, analysed the data, and involved in writing the manuscript; N.H. involved in drafting the manuscript and revising it critically for intellectual content, and is the postgraduate supervisor of first author; H.A. co-supervision of first author, and provided funding for the project. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Nicolette N. Houreld.

Ethics declarations

Competing interests

The authors declare that there is no conflict of interest regarding the publication of this paper.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The material in this paper submitted to Lasers in Medical Science has neither been published, nor is being considered elsewhere for publication.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Jere, S.W., Houreld, N.N. & Abrahamse, H. Effect of photobiomodulation on cellular migration and survival in diabetic and hypoxic diabetic wounded fibroblast cells. Lasers Med Sci 36, 365–374 (2021). https://doi.org/10.1007/s10103-020-03041-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10103-020-03041-y

Keywords

  • Diabetes mellitus
  • Hypoxic
  • Photobiomodulation
  • Wound healing
  • Fibroblasts
  • Signalling pathways