Laser and LED phototherapies on angiogenesis.
Center of Biophotonics, School of Dentistry, Federal University of Bahia, 62 Araújo Pinho Ave, Canela, Salvador, BA, CEP 40140-110, Brazil, email@example.com.
Angiogenesis is a key process for wound healing. There are few reports of LED phototherapy on angiogenesis, mainly in vivo. The aim of the present investigation was to evaluate histologically the angiogenesis on dorsal cutaneous wounds treated with laser (660 and 790 nm) or LEDs (700, 530, and 460 nm) in a rodent model. Twenty-four young adult male Wistar rats weighting between 200 and 250 g were used on the present study. Under general anesthesia, one excisional wound was created on the dorsum of each animal that were then randomly distributed into six groups with four animals each: G0-control; G1-laser 660 nm (60 mW, 2 mm, 10 J/cm(2)); G2-laser 790 nm (50 mW, 2 mm, 10 J/cm(2)); G3-LED 700±20 nm (15 mW, 16 mm, 10 J/cm(2)); G4-LED 530±20 nm (8 mW, 16 mm, 10 J/cm(2)); G5-LED 460±20 nm (22 mW, 16 mm, 10 J/cm(2)). Irradiation started immediately after surgery and was repeated every other day for 7 days. Animal death occurred at the eighth day after surgery. The specimens were removed, routinely processed to wax, cut and stained with HE. Angiogenesis was scored by blood vessel counting in the wounded area. Quantitative results showed that green LED (530±20 nm), red LED (700±20 nm), 790 nm laser and 660 nm laser caused significant increased angiogenesis when compared to the control group. It is concluded that both laser and LED light are capable of stimulating angiogenesis in vivo on cutaneous wounds and that coherence was not decisive on the outcome of the treatment.
J Transl Med. 2010 Feb 16;8:16.
Lasers, stem cells, and COPD.
Lin F, Josephs SF, Alexandrescu DT, Ramos F, Bogin V, Gammill V, Dasanu CA, De Necochea-Campion R, Patel AN, Carrier E, Koos DR.
Entest BioMedical, San Diego, CA, USA.
The medical use of low level laser (LLL) irradiation has been occurring for decades, primarily in the area of tissue healing and inflammatory conditions. Despite little mechanistic knowledge, the concept of a non-invasive, non-thermal intervention that has the potential to modulate regenerative processes is worthy of attention when searching for novel methods of augmenting stem cell-based therapies. Here we discuss the use of LLL irradiation as a “photoceutical” for enhancing production of stem cell growth/chemoattractant factors, stimulation of angiogenesis, and directly augmenting proliferation of stem cells. The combination of LLL together with allogeneic and autologous stem cells, as well as post-mobilization directing of stem cells will be discussed.
Photomed Laser Surg. 2009 Apr;27(2):227-33.
Implantation of low-level laser irradiated mesenchymal stem cells into the infarcted rat heart is associated with reduction in infarct size and enhanced angiogenesis.
Tuby H, Maltz L, Oron U.
Department of Zoology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.
OBJECTIVE: The aim of the present study was to evaluate the possible beneficial effects of implantation of laser-irradiated mesenchymal stem cells (MSCs) into the infarcted rat heart. BACKGROUND DATA: It was demonstrated that low-level laser therapy (LLLT) upregulates cytoprotective factors in ischemic tissues. MATERIALS AND METHODS: MSCs were isolated from rat bone marrow and grown in culture. The cells were laser irradiated with a Ga-Al-As laser (810 nm wavelength), labeled with 5-bromo-2′deoxyuridine (BrdU), and then implanted into infarcted rat hearts. Non-irradiated cells were similarly labeled and acted as controls. Hearts were excised 3 wk later and cells were stained for BrdU and c-kit immunoreactivity. RESULTS: Infarcted hearts that were implanted with laser-treated cells showed a significant reduction of 53% in infarct size compared to hearts that were implanted with non-laser-treated cells. The hearts implanted with laser-treated cells prior to implantation demonstrated a 5- and 6.3-fold significant increase in cell density that positively immunoreacted to BrdU and c-kit, respectively, as compared to hearts implanted with non-laser-treated cells. A significantly 1.4- and 2-fold higher level of angiogenesis and vascular endothelial growth factor, respectively, were observed in infarcted hearts that were implanted with laser-treated cells compared to non-laser-treated implanted cells. CONCLUSION: The findings of the present study provide the first evidence that LLLT can significantly increase survival and/or proliferation of MSCs post-implantation into the ischemic/infarcted heart, followed by a marked reduction of scarring and enhanced angiogenesis. The mechanisms associated with this phenomenon remain to be elucidated in further studies.
Micron. 2009 Jun;40(4):413-8. Epub 2009 Feb 13.
Ultrastructural analysis of the low level laser therapy effects on the lesioned anterior tibial muscle in the gerbil.
Iyomasa DM, Garavelo I, Iyomasa MM, Watanabe IS, Issa JP.
Department of Physiotherapy, São Paulo State University, Presidente Prudente, SP, Brazil.
Low level laser therapy (LLLT) is known for its positive results but studies on the biological and biomodulator characteristics of the effects produced in the skeletal muscle are still lacking. In this study the effects of two laser dosages, 5 or 10 J/cm(2), on the lesioned tibial muscle were compared. Gerbils previously lesioned by 100 g load impact were divided into three groups: GI (n=5) controls, lesion non-irradiated; GII (n=5), lesion irradiated with 5 J/cm(2) and GIII (n=5), lesion irradiated with 10 J/cm(2), and treated for 7 consecutive days with a laser He-Ne (lambda=633 nm). After intracardiac perfusion, the muscles were dissected and reduced to small fragments, post-fixed in 1% osmium tetroxide, dehydrated in increasing alcohol concentrations, treated with propylene oxide and embedded in Spurr resin at 60 degrees C. Ultrafine cuts examined on a transmission electron microscope (Jeol 1010) revealed in the control GI group a large number of altered muscle fibers with degenerating mitochondria, intercellular substance containing degenerating cell fragments and budding blood capillaries with underdeveloped endothelial cells. However, groups GII and GIII showed muscle fibers with few altered myofibrils, regularly contoured mitochondria, ample intermembrane spaces and dilated mitochondrial crests. The clean intercellular substance showed numerous collagen fibers and capillaries with multiple abluminal processes, intraluminal protrusions and several pinocytic vesicles in endothelial cells. It was concluded that laser dosages of 5 or 10 J/cm(2) delivered by laser He-Ne (lambda=633 nm) during 7 consecutive days increase mitochondrial activity in muscular fibers, activate fibroblasts and macrophages and stimulate angiogenesis, thus suggesting effectivity of laser therapy under these experimental conditions.
Lasers Surg Med. 2006 Aug;38(7):682-8.
Modulations of VEGF and iNOS in the rat heart by low level laser therapy are associated with cardioprotection and enhanced angiogenesis.
Tuby H, Maltz L, Oron U.
Department of Zoology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, 69978, Israel.
BACKGROUND AND OBJECTIVES: It has been shown previously that low-level laser therapy (LLLT) significantly reduces infarct size following induction of myocardial infarction in rats and dogs. The aim of the present study was to investigate the effect of LLLT on the expression of vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS). STUDY DESIGN AND
MATERIAL AND METHODS: Myocardial infarction was induced by occlusion of the left descending artery in 87 rats. LLLT was applied to intact and post-infarction. VEGF, iNOS, and angiogenesis were determined.
RESULTS: Both the laser-irradiated rat hearts post-infarction and intact hearts demonstrated a significant increase in VEGF and iNOS expression compared to non-laser-irradiated hearts. LLLT also caused a significant elevation in angiogenesis.
CONCLUSIONS: It is concluded that VEGF and iNOS expression in the infarcted rat heart is markedly upregulated by LLLT and is associated with enhanced angiogenesis and cardioprotection.
|Photomed Laser Surg. 2005 Oct;23(5):470-5.|
Effect of In-Ga-Al-P diode laser irradiation on angiogenesis in partial ruptures of Achilles tendon in rats.
Salate AC, Barbosa G, Gaspar P, Koeke PU, Parizotto NA, Benze BG, Foschiani D.
Department of Physiotherapy, Federal University of Sao Carlos, Sao Paulo, Brazil.
OBJECTIVE: This study was conducted to analyze the effect of different irradiances of low-level laser therapy (LLLT) on angiogenesis after partial rupture of Achilles tendon of rats. BACKGROUND DATA: METHODS: Ninety-six animals were divided into three groups subject to treatment during 3, 5, and 7 days post-lesion. Thirty-two animals were used in each group. The groups were further divided into four subgroups with eight animals in each, receiving In-Ga-Al-P laser (660 nm) treatment at (1) mean output of 10 mW, (2) 40 mW during 10 sec, (3) a sham subgroup, and (4) a non-treatment subgroup. Each animal was subjected to a lesion of the Achilles tendon by dropping a 186-g weight from a 20-cm height over the tendon. Treatment was initiated 6 h post-injury for all the groups. Blood vessels were colored with India ink injection and were examined in a video microscope. RESULTS: Laser exposure promoted an increase in blood vessel count when compared to controls. The 40-mW group showed early neovascularization, with the greatest number of microvessels after three laser applications. The 10-mW subgroup showed angiogenesis activity around the same time as the sham laser group did, but the net number of vessels was significantly higher in the former than in the controls. After seven irradiations, the subgroup receiving 40 mW experienced a drop in microvessel number, but it was still higher than in the control groups. CONCLUSIONS: LLLT of different intensities seems to promote neovascularization in damaged Achilles tendons of rats after partial rupture compared to controls.
Histol Histopathol. 2004 Jan;19(1):43-8.
The effects of low laser irradiation on angiogenesis in injured rat tibiae.
Garavello I, Baranauskas V, da Cruz-Höfling MA.
Department of Semiconductors Instruments, Institute of Biology, State University of Campinas (UNICAMP), Campinas (SP), Brazil.
The influence of He-Ne laser radiation on the formation of new blood vessels in the bone marrow compartment of a regenerating area of the mid-cortical diaphysis of the tibiae of young adult rats was studied. A small hole was surgically made with a dentistry burr in the tibia and the injured area received a daily laser therapy over 7 or 14 days transcutaneously starting 24 h from surgery. Incident energy density dosages of 31.5 and 94.5 Jcm(-2) were applied during the period of the tibia wound healing investigated. Light microscopic examination of histological sections of the injured area and quantification of the newly-formed blood vessels were undertaken. Low-level energy treatment accelerated the deposition of bone matrix and histological characteristics compatible with an active recovery of the injured tissue. He-Ne laser therapy significantly increased the number of blood vessels after 7 days irradiation at an energy density of 94.5 Jcm(-2), but significantly decreased the number of vessels in the 14-day irradiated tibiae, independent of the dosage. These effects were attributed to laser treatment, since no significant increase in blood vessel number was detected between 8 and 15 non-irradiated control tibiae. Molecular mechanisms involved in low-level laser therapy of angiogenesis in post-traumatic bone regeneration needs further investigation.
|Antioxid Redox Signal. 2002 Oct;4(5):785-90.|
Promotion of angiogenesis by low energy laser irradiation.
Mirsky N, Krispel Y, Shoshany Y, Maltz L, Oron U.
The Faculty of Science, Haifa University at Oranim, Tivoon 36006, Israel.
The effect of low energy laser (He-Ne) irradiation (LELI) on the process of angiogenesis in the infarcted rat heart and in the chick chorioallantoic membrane (CAM), as well as the proliferation of endothelial cells in tissue culture, was investigated. Formation of new blood vessels in the infarcted rat heart was monitored by counting proliferating endothelial cells in blood vessels. In the CAM model, defined areas were laser-irradiated or nonirradiated and blood vessel density was recorded in each site in the CAM at various time intervals. Laser irradiation caused a 3.1-fold significant increase in newly formed blood vessels 6 days post infarction, as compared with nonirradiated rats. In the CAM model, a slight inhibition of angiogenesis up to 2 days post irradiation and a significant enhancement of angiogenesis in the laser-irradiated foci as compared with control nonirradiated spots were evident. The LELI caused a 1.8-fold significant increase in the rate of proliferation in endothelial cells in culture over nonirradiated cells. It is concluded that LELI can promote the proliferation of endothelial cells in culture, which may partially explain the augmentation of angiogenesis in the CAM model and in the infarcted heart. These results may have clinical significance by offering therapeutic options to ameliorate angiogenesis in ischemic conditions.