Skip to main content

Advertisement

SpringerLink
Log in

Photobiomodulation effects on keratinocytes cultured in vitro: a critical review

  • Review Article
  • Published:
Lasers in Medical Science Aims and scope Submit manuscript

Abstract

Photobiomodulation therapy (PBMT) has been widely used for the promotion of tissue repair. Despite these therapeutic benefits, in some cases, PBMT appears to be unsuccessful, and the strongest hypothesis is that this failure is due to inadequate light dosimetry and wavelengths. The objective of the present critical review was to evaluate the effects of PBMT on cultured keratinocytes using blue, red, or near-infrared light categorized into arbitrary ranges of energy density (0.1–5.0, 5.1–10.0, 10.1–15.0, and over 15.0 J/cm2). The electronic searches were conducted in PubMed, Web of Science, Scopus and LILACS databases, and included LASER or LED devices. A total of 55 articles evaluating the effects of PBMT on cell viability, proliferation, migration, and cytokine and growth factor production were included. Overall, the studies failed to provide detailed information about light dosimetry or detailed experimental conditions. The vast majority of the energy densities tested produced unmodified results regardless of the wavelength applied. However, it was possible to observe that red and near-infrared light had more stimulatory effects than blue light. In addition, for all parameters analyzed, favorable outcomes were mostly obtained in the range of 0.1–5.0 J/cm2. The less explored energy densities were within the 10.1–15.0 J/cm2 range. Energy densities above 15.0 J/cm2 were ineffective or tended to cause cell death. The heterogeneity of the data does not allow us to define a PBMT range setting protocol that would have beneficial effects on keratinocytes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Diniz IMA, Carreira ACO, Sipert CR, Uehara CM, Moreira MSN, Freire L, Pelissari C, Kossugue PM, de Araújo DR, Sogayar MC, Marques MM (2018) Photobiomodulation of mesenchymal stem cells encapsulated in an injectable rhBMP4-loaded hydrogel directs hard tissue bioengineering. J Cell Physiol 233:4907–4918. https://doi.org/10.1002/jcp.26309

    Article  CAS  PubMed  Google Scholar 

  2. Elad S, Arany P, Bensadoun RJ, Epstein JB, Barasch A, Raber-Durlacher J (2018) Photobiomodulation therapy in the management of oral mucositis: search for the optimal clinical treatment parameters. Support Care Cancer 26:1–3. https://doi.org/10.1007/s00520-018-4262-6

    Article  Google Scholar 

  3. Engel KW, Khan I, Arany PR (2016) Cell lineage responses to photobiomodulation therapy. J Biophotonics 9:1148–1156. https://doi.org/10.1002/jbio.201600025

    Article  CAS  PubMed  Google Scholar 

  4. Anders JJ, Lanzafame RJ, Arany PR (2015) Low-level light/laser therapy versus photobiomodulation therapy. Photomed Laser Surg 33:183–184. https://doi.org/10.1089/pho.2015.9848

    Article  PubMed  PubMed Central  Google Scholar 

  5. Passarella S, Karu T (2014) Absorption of monochromatic and narrow band radiation in the visible and near IR by both mitochondrial and non-mitochondrial photoacceptors results in photobiomodulation. J Photochem Photobiol B 140:344–358. https://doi.org/10.1016/j.jphotobiol.2014.07.021

    Article  CAS  PubMed  Google Scholar 

  6. Arany PR, Cho A, Hunt TD, Sidhu G, Shin K, Hahm E, Huang GX, Weaver J, Chen AC, Padwa BL, Hamblin MR, Barcellos-Hoff MH, Kulkarni AB, J Mooney D (2014) Photoactivation of endogenous latent transforming growth factor–β1 directs dental stem cell differentiation for regeneration. Sci Transl Med 6:238ra69. https://doi.org/10.1126/scitranslmed.3008234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. George S, Hamblin MR, Abrahamse H (2018) Effect of red light and near infrared laser on the generation of reactive oxygen species in primary dermal fibroblasts. J Photochem Photobiol B 188:60–68. https://doi.org/10.1016/j.jphotobiol.2018.09.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ferreira LS, Diniz IMA, Maranduba CMS, Miyagi SPH, Rodrigues MFSD, Moura-Netto C, Marques MM (2018) Short-term evaluation of photobiomodulation therapy on the proliferation and undifferentiated status of dental pulp stem cells. Lasers Med Sci 34(4):659–666. https://doi.org/10.1007/s10103-018-2637-z

    Article  PubMed  Google Scholar 

  9. Kim JE, Woo YJ, Sohn KM, Jeong KH, Kang H (2017) Wnt/β-catenin and ERK pathway activation: a possible mechanism of photobiomodulation therapy with light-emitting diodes that regulate the proliferation of human outer root sheath cells. Lasers Surg Med 49:940–947. https://doi.org/10.1002/lsm.22736

    Article  PubMed  Google Scholar 

  10. Yin K, Zhu R, Wang S, Zhao RC (2017) Low-level laser effect on proliferation, migration, and antiapoptosis of mesenchymal stem cells. Stem Cells Dev 26:762–775. https://doi.org/10.1089/scd.2016.0332

    Article  CAS  PubMed  Google Scholar 

  11. Karu TI (2010) Multiple roles of cytochrome c oxidase in mammalian cells under action of red and IR-A radiation. IUBMB Life 62:607–610. https://doi.org/10.1002/iub.359

    Article  CAS  PubMed  Google Scholar 

  12. Hamblin MR (2018) Mechanisms and mitochondrial redox signaling in photobiomodulation. Photochem Photobiol 94:199–212. https://doi.org/10.1111/php.12864

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hamblin MR (2017) Mechanisms and applications of the anti-inflammatory effects of photobiomodulation. AIMS Biophys 4:337–361. https://doi.org/10.3934/biophy.2017.3.337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mainster MA (2006) Violet and blue light blocking intraocular lenses: photoprotection versus photoreception. Br J Ophthalmol 90:784–792. https://doi.org/10.1136/bjo.2005.086553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wang Y, Huang YY, Wang Y, Lyu P, Hamblin MR (2017) Red (660 nm) or near-infrared (810 nm) photobiomodulation stimulates, while blue (415 nm), green (540 nm) light inhibits proliferation in human adipose-derived stem cells. Sci Rep 7:7781. https://doi.org/10.1038/s41598-017-07525-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. da Silva JP, da Silva MA, Almeida APF, Junior IL, Matos AP (2010) Laser therapy in the tissue repair process: a literature review. Photomed Laser Surg 28:17–21. https://doi.org/10.1089/pho.2008.2372

    Article  PubMed  Google Scholar 

  17. Basso FG, Soares DG, Pansani TN, Cardoso LM, Scheffel DL, de Souza Costa CA, Hebling J (2016) Proliferation, migration, and expression of oral-mucosal-healing-related genes by oral fibroblasts receiving low-level laser therapy after inflammatory cytokines challenge. Lasers Surg Med 48:1006–1014. https://doi.org/10.1002/lsm.22553

    Article  PubMed  Google Scholar 

  18. Houreld NN, Ayuk SM, Abrahamse H (2014) Expression of genes in normal fibroblast cells (WS1) in response to irradiation at 660 nm. J Photochem Photobiol B 130:146–152. https://doi.org/10.1016/j.jphotobiol.2013.11.018

    Article  CAS  PubMed  Google Scholar 

  19. Rizzi M, Migliario M, Tonello S, Rocchetti V, Renò F (2018) Photobiomodulation induces in vitro re-epithelialization via nitric oxide production. Lasers Med Sci 33:1–6. https://doi.org/10.1007/s10103-018-2443-7

    Article  Google Scholar 

  20. Solmaz H, Ulgen Y, Gulsoy M (2017) Photobiomodulation of wound healing via visible and infrared laser irradiation. Lasers Med Sci 32:903–910. https://doi.org/10.1007/s10103-017-2191-0

    Article  PubMed  Google Scholar 

  21. Tata DB, Waynant RW (2011) Laser therapy: a review of its mechanism of action and potential medical applications. Laser Photonics Rev 5:1–12. https://doi.org/10.1002/lpor.200900032

    Article  CAS  Google Scholar 

  22. AlGhamdi KM, Kumar A, Moussa NA (2012) Low-level laser therapy: a useful technique for enhancing the proliferation of various cultured cells. Lasers Med Sci 27:237–249. https://doi.org/10.1007/s10103-011-0885-2

    Article  PubMed  Google Scholar 

  23. Marques MM, de Cara SPHM, Abe GL, Pedroni ACF, Diniz IMA, Moreira MS (2017) Effects of photobiomodulation therapy in dentoalveolar-derived mesenchymal stem cells: a review of literature. Laser Dent Sci 1:1–7. https://doi.org/10.1007/s41547-017-0002-3

    Article  Google Scholar 

  24. Peplow PV, Chung TY, Baxter GD (2010) Laser photobiomodulation of proliferation of cells in culture: a review of human and animal studies. Photomed Laser Surg Suppl 1:S3–S40. https://doi.org/10.1089/pho.2010.2771

    Article  Google Scholar 

  25. World Association of Laser Therapy (WALT) (2006) Consensus agreement on the design and conduct of clinical studies with low-level laser therapy and light therapy for musculoskeletal pain and disorders. Photomed Laser Surg 24:761–762. https://doi.org/10.1089/pho.2006.24.761

    Article  Google Scholar 

  26. Rooney AA, Boyles AL, Wolfe MS, Bucher JR, Thayer KA (2014) Systematic review and evidence integration for literature-based environmental health science assessments. Environ Health Perspect 122:711–718. https://doi.org/10.1289/ehp.1307972

    Article  PubMed  PubMed Central  Google Scholar 

  27. Basso FG, Oliveira CF, Kurachi C, Hebling J, de Souza Costa CA (2013) Biostimulatory effect of low-level laser therapy on keratinocytes in vitro. Lasers Med Sci 28:367–374. https://doi.org/10.1007/s10103-012-1057-8

    Article  PubMed  Google Scholar 

  28. Sperandio FF, Simões A, Corrêa L, Aranha AC, Giudice FS, Hamblin MR, Sousa SC (2015) Low-level laser irradiation promotes the proliferation and maturation of keratinocytes during epithelial wound repair. J Biophotonics 8:795–803. https://doi.org/10.1002/jbio.201400064

    Article  CAS  PubMed  Google Scholar 

  29. Castellano-Pellicena I, Uzunbajakava NE, Mignon C, Raafs B, Botchkarev VA, Thornton MJ (2018) Does blue light restore human epidermal barrier function via activation of opsin during cutaneous wound healing? Lasers Surg Med 51(4):370–382. https://doi.org/10.1002/lsm.23015

    Article  PubMed  Google Scholar 

  30. Walter C, Pabst AM, Ziebart T (2015) Effects of a low-level diode laser on oral keratinocytes, oral fibroblasts, endothelial cells and osteoblasts incubated with bisphosphonates: an in vitro study. Biomed Rep 3:14–18. https://doi.org/10.3892/br.2014.389

    Article  PubMed  Google Scholar 

  31. Trachootham D, Alexandre J, Huang P (2009) Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov 8:579–591. https://doi.org/10.1038/nrd2803

    Article  CAS  PubMed  Google Scholar 

  32. Gagnon D, Gibson TW, Singh A, zur Linden AR, Kazienko JE, LaMarre J (2016) An in vitro method to test the safety and efficacy of low-level laser therapy (LLLT) in the healing of a canine skin model. BMC Vet Res 12:73. https://doi.org/10.1186/s12917-016-0689-5

    Article  PubMed  PubMed Central  Google Scholar 

  33. Lee JB, Bae SH, Moon KR, Na EY, Yun SJ, Lee SC (2016) Light-emitting diodes downregulate cathelicidin, kallikrein and toll-like receptor 2 expressions in keratinocytes and rosacea-like mouse skin. Exp Dermatol 25:956–961. https://doi.org/10.1111/exd.13133

    Article  CAS  PubMed  Google Scholar 

  34. Liebmann J, Born M, Kolb-Bachofen V (2010) Blue-light irradiation regulates proliferation and differentiation in human skin cells. J Invest Dermatol 130:259–269. https://doi.org/10.1038/jid.2009.194

    Article  CAS  PubMed  Google Scholar 

  35. Migliario M, Rizzi M, Rocchetti V, Cannas M, Renò F (2013) In vitro toxicity of photodynamic antimicrobial chemotherapy on human keratinocytes proliferation. Lasers Med Sci 28:565–569. https://doi.org/10.1007/s10103-012-1112-5

    Article  PubMed  Google Scholar 

  36. Szeimies RM, Abels C, Fritsch C, Karrer S, Steinbach P, Bäumler W, Goerz G, Goetz AE, Landthaler M (1995) Wavelength dependency of photodynamic effects after sensitization with 5-aminolevulinic acid in vitro and in vivo. J Invest Dermatol 105:672–677. https://doi.org/10.1111/1523-1747.ep12324377

    Article  CAS  PubMed  Google Scholar 

  37. Opal SM, Depalo V (2000) Anti-inflammatory cytokines. Chest 117:1162–1172. https://doi.org/10.1378/chest.117.4.1162

    Article  CAS  PubMed  Google Scholar 

  38. Fushimi T, Inui S, Nakajima T, Ogasawara M, Hosokawa K, Itami S (2012) Green light emitting diodes accelerate wound healing: characterization of the effect and its molecular basis in vitro and in vivo. Wound Repair Regen 20:226–235. https://doi.org/10.1111/j.1524-475X.2012.00771.x

    Article  PubMed  Google Scholar 

  39. Haas AF, Wong JW, Iwahashi CK, Halliwell B, Cross CE, Davis PA (1998) Redox regulation of wound healing? NF-kappaB activation in cultured human keratinocytes upon wounding and the effect of low energy HeNe irradiation. Free Radic Biol Med 25:998–1005. https://doi.org/10.1016/S0891-5849(98)00135-X

    Article  CAS  PubMed  Google Scholar 

  40. Yu HS, Chang KL, Yu CL, Chen JW, Chen GS (1996) Low-energy helium-neon laser irradiation stimulates interleukin-1 alpha and interleukin-8 release from cultured human keratinocytes. J Invest Dermatol 107:593–596. https://doi.org/10.1111/1523-1747.ep12583090

    Article  CAS  PubMed  Google Scholar 

  41. Feliciani C, Gupta AK, Saucier DN (1996) Keratinocytes and cytokine/growth factors. Crit Rev Oral Biol Med 7:300–318

    Article  CAS  Google Scholar 

  42. Baroni A, De Filippis A, Oliviero G, Fusco A, Perfetto B, Buommino E, Donnarumma G (2017) Effect of 1064-nm Q-switched Nd: YAG laser on invasiveness and innate immune response in keratinocytes infected with Candida albicans. Lasers Med Sci 33:941–948. https://doi.org/10.1007/s10103-017-2407-3

    Article  PubMed  Google Scholar 

  43. Lim W, Kim J, Lim C, Kim S, Jeon S, Karna S, Cho M, Choi H, Kim O (2012) Effect of 635 nm light-emitting diode irradiation on intracellular superoxide anion scavenging independent of the cellular enzymatic antioxidant system. Photomed Laser Surg 30:451–459. https://doi.org/10.1089/pho.2011.3199

    Article  CAS  PubMed  Google Scholar 

  44. Mignon C, Uzunbajakava NE, Raafs B, Botchkareva NV, Tobin DJ (2017) Photobiomodulation of human dermal fibroblasts in vitro: decisive role of cell culture conditions and treatment protocols on experimental outcome. Sci Rep 7:2797. https://doi.org/10.1038/s41598-017-02802-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Tucker LD, Lu Y, Dong Y, Yang L, Li Y, Zhao N, Zhang Q (2018) Photobiomodulation therapy attenuates hypoxic-ischemic injury in a neonatal rat model. J Mol Neurosci 65:514–526. https://doi.org/10.1007/s12031-018-1121-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

Mrs. E. Greene provided English editing of the manuscript.

Funding

This study was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Finance Code 001) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). T.A.S. and R.A.M. are CNPq research fellows. P.T.R.A. and J.A.A.A. are the recipients of fellowships.

Author information

Authors and Affiliations

  1. Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

    Priscila Thaís Rodrigues de Abreu, José Alcides Almeida de Arruda, Ricardo Alves Mesquita & Tarcília Aparecida Silva

  2. Department of Pediatric Dentistry and Orthodontics, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

    Lucas Guimarães Abreu

  3. Department of Restorative Dentistry, School of Dentistry, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, 31270-901, Brazil

    Ivana Márcia Alves Diniz

Authors
  1. Priscila Thaís Rodrigues de Abreu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. José Alcides Almeida de Arruda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ricardo Alves Mesquita
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lucas Guimarães Abreu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ivana Márcia Alves Diniz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tarcília Aparecida Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ivana Márcia Alves Diniz.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Ethical approval is not applicable in this study.

Additional information

Publisher’s note

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

Electronic supplementary material

Supplementary Table 1

(DOCX 32.5 kb)

Supplementary Table 2

(DOCX 35.3 kb)

Supplementary Table 3

(DOCX 57.8 kb)

Supplementary Table 4

(DOCX 39.3 kb)

Supplementary Table 5

(DOCX 31.9 kb)

Supplementary References 1

(DOCX 23 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Abreu, P.T.R., de Arruda, J.A.A., Mesquita, R.A. et al. Photobiomodulation effects on keratinocytes cultured in vitro: a critical review. Lasers Med Sci 34, 1725–1734 (2019). https://doi.org/10.1007/s10103-019-02813-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10103-019-02813-5

Keywords

Search

Navigation