Medical applications of space light-emitting diode technology-space station and beyond

Journal ArticleSpace light-emitting diode (LED) technology has provided medicine with a new tool capable of delivering light deep into tissues of the body, at wavelengths which are biologically optimal for cancer treatment and wound healing. This LED technology has already flown on Space Shuttle missions, and shows promise for wound healing applications of benefit to Space Station astronauts

Benzoporphyrin derivative and light-emitting diode for use in photodynamic therapy: applications of space light-emitting diode technology

Journal ArticlePhotodynamic therapy (PDT) is a cancer treatment modality that recently has been applied as adjuvant therapy for rain tumors. PDT consists of intravenously injecting a photosensitizer, which preferentially accumulates in tumor ells, into a patient and then activating the photosensitizer with a light source. This results in free radical generation ollowed by cell death. The development of more effective light sources for PDT of brain tumors has been facilitated by applications of space light-emitting diode array technology; thus permitting deeper tumor penetration of light and use of better photosensitizers. Currently, the most commonly used photosensitizer for brain tumor PDT is Photofrin®. Photofrin® is a heterogeneous mixture of compounds derived from hematoporphyrin. Photofrin® is ctivated with a 630 nm laser light and does destroy tumor cells in animal models and humans. However, treatment "ailure does occur using this method. Most investigators attribute this failure to the limited penetration of brain tissue by a 630 nm laser light and to the fact that Photofrin® has only a minor absorption peak at 630 nm, meaning that only a small fraction of the chemical is activated. Benzoporphyrin Derivative Monoacid Ring A (BPD) is a new, second generation photosensitizer that can potentially improve PDT for brain tumors. BPD has a major absorption peak at 690 nm, which gives it two distinct advantages over Photofrin®. First, longer wavelengths of light penetrate brain tissue more easily so that larger tumors could be treated, and second, the major absorption peak means that a larger fraction of the drug is activated upon exposure to light. In the first part of this project we have tudied the tumoricidal effects of BPD in vitro using 2A9 canine glioma and U373 human glioblastoma cell cultures. Using light emitting diodes (LED) with a peak emission of 688 nm as a light source, cell kill of up to 86 percent was measured in these cell lines by tumor DNA synthesis reduction. The effectiveness of BPD against tumor cells in vitro thus established, we have taken the first step toward determining its effectiveness in vivo. The second part of this project consisted of experiments performed to determine the maximum tolerated dose (MTD) of both BPD and LED light. At a light dose of 100 J/cm^2, skin damage and neurotoxicity were seen at a BPD dose of 1.0 mg/kg, but not at a dose of 0.75 mg/kg. When BPD remained constant at 0.75 mg/kg, skin damage was seen at light dosages of 125 J/cm^2, 150 J/cm^2 and 175 J/cm^2. One dog also died at a light dose of 175 J/cm^2. Further studies will be needed to determine the effectiveness of BPD against tumor cells in vivo

Photodynamic therapy

Journal ArticleWe appreciate the comments of Drs. Kaye and Hill on our article. We are pleased that these investigators concurred with our impression that photodynamic therapy (PDT) may potentially be useful in the treatment of posterior fossa tumors. Several interesting questions were raised about the technical aspects of our method of determining tissue Photofrin levels in tumor and surrounding normal brain. Our laboratory concurs with their feelings about the limitations of relative fluorescence. We have therefore conducted additional investigations with radiolabeled Photofrin to quantify tissue levels by yet another technique

Role of photodynamic therapy in posterior fossa brain tumors: a preclinical study in a canine glioma model

Journal ArticlePhotodynamic therapy was studied in dogs with and without posterior fossa glioblastomas. This mode of therapy consisted of intravenous administration of Photofrin-II at doses ranging from 0.75 to 4 mg/kg 24 hours prior to laser light irradiation in the posterior fossa. Tissue levels of Photofrin-lI were four times greater in the tumor than in the surrounding normal brain. Irradiation was performed using 1 hour of 500 mW laser light at a wavelength of 630 nm delivered through a fiberoptic catheter directly into the tumor bed via a burr hole. All animals receiving a high dose (4 or 2 mg/kg) of Photofrin-II developed serious brain-stem neurotoxicity resulting in death or significant residual neurological deficits. A lower dose (0.75 mg/kg) of Photofrin-II produced tumor kill without significant permanent brain-stem toxicity in either the control animals or the animals with cerebellar brain tumors receiving photodynamic therapy

NASA light-emitting diode medical program-progress in space flight and terrestrial applications

Journal ArticleThis work is supported and managed through the NASA Marshall Space Flight Center - SBIR Program. Studies on cells exposed to microgravity and hypergravity indicate that human cells need gravity to stimulate cell growth. As the gravitational force increases or decreases, the cell function responds in a linear fashion. This poses significant health risks for astronauts in long termspace flight. LED-technology developed for NASA plant growth experiments in space shows promise for delivering light deep into tissues of the body to promote wound healing and human tissue growth. This LED-technology is also biologically optomal for photodynamic therapy of cancer

Effect of Photobiomodulation on Vinblastine-Poisoned Murine HERS Cells

Objective: The aim of this study was to investigate the effect of near-infrared (NIR) photobiomodulation on the proliferation and glutathione levels in murine Hertwig\u27s epithelial root sheath (HERS) cells after poisoning with vinblastine. Background: Photobiomodulation has been shown to improve wound healing in a number of animal models. There have been no studies on the effect of photobiomodulation on cancer-related chemotherapy injury to the cells that initiate tooth root growth. Materials and Methods: Control groups consisted of murine HERS cells without vinblastine (VB−) and cells with vinblastine at 10, 20, and 30 ng/mL (VB10, VB20, and VB30). Experimental groups consisted of these same groups with light therapy (VB-L, VB10L, VB20L, and VB30L). The cells were exposed to vinblastine for 1 h. Photobiomodulation consisted of a 75-cm2 gallium-aluminum-arsenide light-emitting diode (LED) array at an energy density of 12.8 J/cm2, delivered with 50 mW/cm2 power over 256 s. Results: Vinblastine alone significantly decreased HERS cell proliferation and glutathione levels at all concentrations (VB10 [−55%, p \u3c 1.0 × 10−8]; VB20 [−72%, p \u3c 1.0 × 10−9]; VB30 [−80%, p \u3c 1.0 × 10−10]; and VB10 [−36%, p \u3c 0.0001]; VB20 [−49%, p \u3c 1.0 × 10−6]; VB30 [−53%, p \u3c 1.0 × 10−7] respectively). Photobiomodulation significantly increased cell proliferation at all levels of vinblastine exposure (VB10L [+50%, p \u3c 0.0001]; VB20L [+45%, p \u3c 0.05]; VB30 [+39%, p \u3c 0.05]) but not of the control (+22%, p  = 0.063). The photobiomodulation significantly increased glutathione production in all concentrations of vinblastine except 20 ng/mL (VB10L [+39%, p = 0.007]; VB20L [+19%, p = 0.087]; VB30 [+14%, p = 0.025]) and the control (+12%, p = 0.13). Conclusions: Photobiomodulation demonstrated an improvement in proliferation and glutathione levels in vinblastine-poisoned murine HERS cells

NASA Light-Emitting Diodes for the Prevention of Oral Mucositis in Pediatric Bone Marrow Transplant Patients

Objective: The purpose of this study was to determine the effects of prophylactic near-infrared light therapy from light-emitting diodes (LEDs) in pediatric bone marrow transplant (BMT) recipients. Background Data: Oral mucositis (OM) is a frequent side effect of chemotherapy that leads to increased morbidity. Near-infrared light has been shown to produce biostimulatory effects in tissues, and previous results using nearinfrared lasers have shown improvement in OM indices. However, LEDs may hold greater potential for clinical applications. Materials and Methods: We recruited 32 consecutive pediatric patients undergoing myeloablative therapy in preparation for BMT. Patients were examined by two of three pediatric dentists trained in assessing the Schubert oral mucositis index (OMI) for left and right buccal and lateral tongue mucosal surfaces, while the patients were asked to rate their current left and right mouth pain, left and right xerostomia, and throat pain. LED therapy consisted of daily treatment at a fluence of 4 J/cm2 using a 670-nm LED array held to the left extraoral epithelium starting on the day of transplant, with a concurrent sham treatment on the right. Patients were assessed before BMT and every 2–3 days through posttransplant day 14. Outcomes included the percentage of patients with ulcerative oral mucositis (UOM) compared to historical epidemiological controls, the comparison of left and right buccal pain to throat pain, and the comparison between sides of the buccal and lateral tongue OMI and buccal pain. Results: The incidence of UOM was 53%, compared to an expected rate of 70–90%. There was also a 48% and 39% reduction of treated left and right buccal pain, respectively, compared to untreated throat pain at about posttransplant day 7 (p \u3c 0.05). There were no significant differences between sides in OMI or pain. Conclusion: Although more studies are needed, LED therapy appears useful in the prevention of OM in pediatric BMT patients

NASA Light Emitting Diode Medical Applications from Deep Space to Deep Sea

This work is supported and managed through the NASA Marshall Space Flight Center-SBIR Program. LED-technology developed for NASA plant growth experiments in space shows promise for delivering light deep into tissues of the body to promote wound healing and human tissue growth. We present the results of LED-treatment of cells grown in culture and the effects of LEDs on patients’ chronic and acute wounds. LED-technology is also biologically optimal for photodynamic therapy of cancer and we discuss our successes using LEDs in conjunction with light-activated chemotherapeutic drugs

Effect of NASA Light-emitting Diode Irradiation on Wound Healing

Objective: The purpose of this study was to assess the effects of hyperbaric oxygen (HBO) and near-infrared light therapy on wound healing. Background Data: Light-emitting diodes (LED), originally developed for NASA plant growth experiments in space show promise for delivering light deep into tissues of the body to promote wound healing and human tissue growth. In this paper, we review and present our new data of LED treatment on cells grown in culture, on ischemic and diabetic wounds in rat models, and on acute and chronic wounds in humans. Materials and Methods: In vitro and in vivo (animal and human) studies utilized a variety of LED wavelength, power intensity, and energy density parameters to begin to identify conditions for each biological tissue that are optimal for biostimulation. Results: LED produced in vitro increases of cell growth of 140–200% in mouse-derived fibroblasts, rat-derived osteoblasts, and rat-derived skeletal muscle cells, and increases in growth of 155–171% of normal human epithelial cells. Wound size decreased up to 36% in conjunction with HBO in ischemic rat models. LED produced improvement of greater than 40% in musculoskeletal training injuries in Navy SEAL team members, and decreased wound healing time in crew members aboard a U.S. Naval submarine. LED produced a 47% reduction in pain of children suffering from oral mucositis. Conclusion: We believe that the use of NASA LED for light therapy alone, and in conjunction with hyperbaric oxygen, will greatly enhance the natural wound healing process, and more quickly return the patient to a preinjury/ illness level of activity. This work is supported and managed through the NASA Marshall Space Flight Center–SBIR Program