Wound healing stimulation in mice by low-level light

It has been known for many years that low levels of laser or non-coherent light (LLLT) accelerate some phases of wound healing. LLLT can stimulate fibroblast and keratinocyte proliferation and migration. It is thought to work via light absorption by mitochondrial chromophores leading to an increase in ATP, reactive oxygen species and consequent gene transcription. However, despite many reports about the positive effects of LLLT on wound healing, its use remains controversial. Our laboratory has developed a model of a full thickness excisional wound in mice that allows quantitative and reproducible light dose healing response curves to be generated. We have found a biphasic dose response curve with a maximum positive effect at 2 J/cm2 of 635-nm light and successively lower beneficial effects from 3-25 J/cm2, the effect is diminished at doses below 2J/cm2 and gradually reaches control healing levels. At light doses above 25 J/cm2 healing is actually worse than controls. The two most effective wavelengths of light were found to be 635 and 820-nm. We found no difference between filtered 635±15-nm light from a lamp and 633-nm light from a HeNe laser. The strain and age of the mouse affected the magnitude of the effect. Light treated wounds start to contract after illumination while control wounds initially expand for the first 24 hours. Our hypothesis is that a single brief light exposure soon after wounding affects fibroblast cells in the margins of the wound. Cells may be induced to proliferate, migrate and assume a myofibroblast phenotype. Our future work will be focused on understanding the mechanisms underlying effects of light on wound healing processes.

[1]  B. Hinz,et al.  Alpha-smooth muscle actin expression upregulates fibroblast contractile activity. , 2001, Molecular biology of the cell.

[2]  H Abrahamse,et al.  Biological effects of helium-neon laser irradiation on normal and wounded human skin fibroblasts. , 2005, Photomedicine and laser surgery.

[3]  Márcia Martins Marques,et al.  Effect of low‐power laser irradiation on cell growth and procollagen synthesis of cultured fibroblasts , 2002, Lasers in surgery and medicine.

[4]  T. Karu,et al.  Exact action spectra for cellular responses relevant to phototherapy. , 2005, Photomedicine and laser surgery.

[5]  N. Cullum,et al.  A systematic review of laser therapy for venous leg ulcers. , 1999, Journal of wound care.

[6]  R. Diegelmann,et al.  Wound healing: an overview of acute, fibrotic and delayed healing. , 2004, Frontiers in bioscience : a journal and virtual library.

[7]  A Crooks,et al.  How does ageing affect the wound healing process? , 2005, Journal of wound care.

[8]  N. Quan,et al.  Impaired wound contraction and delayed myofibroblast differentiation in restraint-stressed mice , 2005, Brain, Behavior, and Immunity.

[9]  A B West,et al.  Myofibroblasts. I. Paracrine cells important in health and disease. , 1999, The American journal of physiology.

[10]  J. Uitto,et al.  Biostimulation of Wound Healing in Vivo by a Helium-Neon Laser , 1987, Annals of plastic surgery.

[11]  J. Kana,et al.  Effect of low-power density laser radiation on healing of open skin wounds in rats. , 1981, Archives of surgery.

[12]  J C Franquin,et al.  Helium-neon laser treatment transforms fibroblasts into myofibroblasts. , 1990, The American journal of pathology.

[13]  D M Bissell,et al.  The role of alpha1beta1 integrin in wound contraction. A quantitative analysis of liver myofibroblasts in vivo and in primary culture. , 1997, The Journal of biological chemistry.

[14]  Kenneth A. Arndt,et al.  Low‐Level Laser Therapy for Wound Healing: Mechanism and Efficacy , 2005, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[15]  Hakim K. Said,et al.  The future of wound healing: pursuing surgical models in transgenic and knockout mice. , 2004, Journal of the American College of Surgeons.

[16]  Alena R A P Medrado,et al.  Influence of low level laser therapy on wound healing and its biological action upon myofibroblasts , 2003, Lasers in surgery and medicine.

[17]  Todd A McLoda,et al.  Low-Level Laser Therapy Facilitates Superficial Wound Healing in Humans: A Triple-Blind, Sham-Controlled Study. , 2004, Journal of athletic training.

[18]  D. Cambier,et al.  Increased fibroblast proliferation induced by light emitting diode and low power laser irradiation , 2003, Lasers in Medical Science.

[19]  D. Kopera,et al.  Low level laser: does it influence wound healing in venous leg ulcers? A randomized, placebo‐controlled, double‐blind study , 2005, The British journal of dermatology.

[20]  Subburaman Mohan,et al.  New quantitative trait loci that regulate wound healing in an intercross progeny from DBA/1J and 129×1/SvJ inbred strains of mice , 2006, Functional & Integrative Genomics.

[21]  Shizhong Xu,et al.  Genetic control of the rate of wound healing in mice , 2001, Heredity.

[22]  P. Kolari,et al.  Comparative effects of exposure to different light sources (He-Ne laser, InGaAl diode laser, a specific type of noncoherent LED) on skin blood flow for the head. , 1996, Acupuncture & electro-therapeutics research.

[23]  T I Karu A suitable model for wound healing: How many times are we to stumble over the same block? , 1999, Lasers in surgery and medicine.

[24]  A B West,et al.  Myofibroblasts: paracrine cells important in health and disease. , 2000, Transactions of the American Clinical and Climatological Association.

[25]  M. D. Lucroy,et al.  Effect of wavelength on low‐intensity laser irradiation‐stimulated cell proliferation in vitro , 2005, Lasers in surgery and medicine.

[26]  Paul Martin,et al.  Impaired wound healing in embryonic and adult mice lacking vimentin. , 2000, Journal of cell science.