Harvard Clinical Trial Proves Lasers Activate Stem Cells to Regenerate Tissue


Harvard’s groundbreaking new research in the use of lasers to stimulate stem cells to regrow tissue is generating interest and excitement throughout the medical community.

A recent study led by Harvard University’s Wyss Institute has done more than just demonstrate that lasers can activate the process that causes stem cells to differentiate and promote tissue regeneration; they have proven the molecular mechanism by which the tissue can be grown. Dr. Praveen R. Arany, lead author and dentist, and his team drilled holes in the molars of rodents, treated the pulp of the teeth with five minutes of laser and confirmed with microscopy and x-ray imaging that just twelve weeks later the stem cells differentiated and formed dentin, a primary component of a tooth. Tissue was regenerated using the body’s own mechanisms rather than extracting stem cells and facilitating growth in a laboratory setting as is common today. By demonstrating a clear process for regeneration, this team of scientists has laid the groundwork for subsequent human trials and solutions for many of today’s problematic medical conditions.

stem cells generated by laserWyss Institute reports that “the research, led by David J. Mooney, Professor of Bioengineering at the Harvard School of Engineering and Applied Sciences (SEAS), lays the foundation for a host of clinical applications … such as wound healing, bone regeneration, and more.” 1 In a Boston Globe report on the study (May 28, 2014), Dr. Jonathan Garlick, Director of the Center for Integrated Tissue Engineering at the Tufts University School of Dental Medicine, said “I think this has very broad applications.” He referred to the research as “a powerful proof of concept” that is “very relevant directly in a variety of different tissues that require stimulation and activation of healing and repair – such as chronic foot ulcers in diabetic patients, bone healing, and bone regeneration.”2

Several studies have been conducted on animals which provide proof of concept. The Curalase laser has an FDA clearance of Non-Significant Risk to treat PATIENTS for the pain associated with backs, knees and neuropathy. While treating the burning pain of neuropathy, the return of feeling, improved circulation and accelerated wound healing were noted. When treating the pain associated with fibromyalgia, after the first treatment many patients experienced a significant decrease in pain. After the first week of treatments, patients report the ability to sleep through the night along with an enhanced sense of general wellbeing. The pain associated with such conditions is alleviated as the tissue heals. For over eight years, Curalase has maintained a success rate of 87% and treated greater than 6,000 patients.

The use of laser energy to relieve pain by regenerating tissue has enormous potential that will drive future research.

Photoactivation of Endogenous Latent Transforming Growth Factor–β1 Directs Dental Stem Cell Differentiation for Regeneration

Praveen R. Arany, Andrew Cho, Tristan D. Hunt, Gursimran Sidhu, Kyungsup Shin, Eason Hahm,
George X. Huang, James Weaver, Aaron Chih-Hao Chen, Bonnie L. Padwa, Michael R. Hamblin,
Mary Helen Barcellos-Hoff, Ashok B. Kulkarni, David J. Mooney


Rapid advancements in the field of stem cell biology have led to many current efforts to exploit stem cells as therapeutic agents in regenerative medicine. However, current ex vivo cell manipulations common to most regenerative approaches create a variety of technical and regulatory hurdles to their clinical translation, and even simpler approaches that use exogenous factors to differentiate tissue-resident stem cells carry significant off-target side effects. We show that non-ionizing, low-power laser (LPL) treatment can instead be used as a minimally invasive tool to activate an endogenous latent growth factor complex, transforming growth factor–β1 (TGF-β1), that subsequently differentiates host stem cells to promote tissue regeneration. LPL treatment induced reactive oxygen species (ROS) in a dose-dependent manner, which, in turn, activated latent TGF-β1 (LTGF-β1) via a specific methionine residue (at position 253 on LAP). Laser-activated TGF-β1 was capable of differentiating human dental stem cells in vitro. Further, an in vivo pulp capping model in rat teeth demonstrated significant increase in dentin regeneration after LPL treatment. These in vivo effects were abrogated in TGF-β receptor II (TGF-βRII) conditional knockout (DSPPCreTGF-βRIIfl/fl) mice or when wild-type mice were given a TGF-βRI inhibitor. These findings indicate a pivotal role for TGF-β in mediating LPL-induced dental tissue regeneration. More broadly, this work outlines a mechanistic basis for harnessing resident stem cells with a light-activated endogenous cue for clinical regenerative applications.

  • Copyright © 2014, American Association for the Advancement of Science

Citation: P. R. Arany, A. Cho, T. D. Hunt, G. Sidhu, K. Shin, E. Hahm, G. X. Huang, J. Weaver, A. C. Chen, B. L. Padwa, M. R. Hamblin, M. H. Barcellos-Hoff, A. B. Kulkarni, D. J. Mooney, Photoactivation of Endogenous Latent Transforming Growth Factor–β1 Directs Dental Stem Cell Differentiation for Regeneration. Sci. Transl. Med. 6, 238ra69 (2014).

Sci Transl Med. 2014 May 28;6(238):238ra69. doi: 10.1126/scitranslmed.3008234


Citations/Related Articles:

1 Harvard, “Researchers use light to coax stem cells to repair teeth”, Kristen Kusek, Wyss Institute, May 28, 2014

2 Boston Globe, “Laser light triggers stem cells to regrow teeth”, Carolyn Y. Johnson, Globe Staff, May 28, 2014

Laser Stimulation of Stem Cells Repairs Kidney and Liver Damage – Sheds Light on How Laser Therapy Heals


Stem cells stimulated with laser irradiation can do more than just reduce scar tissue in rat hearts after heart attack (Tuby, H. et al, 2011); additional studies show that stem cells can rejuvenate rat liver and rat kidney, and even migrate from bone marrow to the ischemia-reperfusion injury in the kidney resulting in improved organ function. Is this proof-of-concept for an underlying mechanism by which laser therapy, used to relieve pain in the lower back, knees or joints, could be repairing bone or muscle tissue?

Laser stimulation of stem cells, tissue regeneration, tissue repair

Rat Kidney
(photo by M. Bahe)

In a 2014 study reported in the Journal of Biomedical Science and Engineering, researchers sought to investigate the potential benefits of laser stimulated stem cells in a rat model of renal failure since there are few treatment options currently available for this life-threatening disease. They induced an ischemia-reperfusion injury in the kidneys of rats and then evaluated the effect of laser therapy applied to the bone marrow. Results showed restoration of renal tubules and reduced necrosis in the laser-treated rats as compared to the control group. Researchers concluded that the laser stimulation of the bone marrow caused an increase in the density of mesenchymal stem cells in the kidneys and thus an increase in kidney function.

In a 2010 study conducted at Tel-Aviv University, Professor Uri Oron and his team applied laser irradiation to stem cells in 12 rats that had undergone removal of 70% of their livers for experimental purposes. Results showed a significant increase in the number of proliferating (stem) cells in the regenerating parts of the laser-treated livers compared to the non-treated livers. Furthermore, researchers observed an increase in density of newly formed blood vessels. Did these new blood vessels contribute to tissue repair and healing? Wound healing is similarly marked by the formation of granulation tissue complete with tiny capillaries and new connective tissue.

Patients suffering from diseases that either threaten life or limit its quality are anxious to see more clinical studies like these advance to human trials in order to prove the efficacy of new treatments like laser stimulation of bone marrow.

Induction of Autologous Bone-Marrow Stem Cells by Low-Level Laser Therapy Has Beneficial Effects on the Kidneys Post-Ischemia-Reperfusion Injury in the Rat

Authors: Hana Tuby, Lidya Maltz, Uri Oron

Citation: Journal of Biomedical Science and Engineering (2014), 7, 453-463. doi: 10.4236/jbise.2014.78048.

Acute renal failure has a 50% – 80% mortality rate. Currently, treatment options for this life-threatening disease are limited. Low-level laser therapy (LLLT) has been found to modulate biological activity. The aim of the present study was to investigate the possible beneficial effects of laser application to stem cells in the bone marrow, on the kidneys of rats that had undergone ischemia-reperfusion injury (IRI). IRI was induced by occlusion of the renal artery to 3- and 7-month-old rats for 15 or 30 minutes. In an additional experiment IRI was applied to both kidneys for 20 min each in 2-3-month-old rats. Rats were then divided randomly into two groups of control and laser-treated. Laser therapy (Ga-Al-As 810 nm, 200 mW output for 2 min) was applied to the bone marrow 1 and 7 days post-IRI to the kidneys, and rats were sacrificed 2 weeks later. Histomorphometry and immunohistochemistry were performed on kidney sections and blood markers for kidney function. Quantitative histomorphometric analysis revealed a reduction in dilatation of the renal tubules, restored structural integrity of the renal tubules, and reduced necrosis in the laser-treated rats as compared to the control, non-laser-irradiated group. C-kit positive cell density in kidneys post-IRI and laser-treatment was significantly (p = 0.015) 3.2-fold higher compared to the control group. Creatinine and blood urea nitrogen content were significantly lower in the laser-treated rats as compared to control. It is concluded that LLLT application to the bone marrow (BM) causes a significant increase in the density of mesenchymal stem cells in the kidneys post-IRI, probably by induction of stem cells in the BM, which subsequently migrate to the IRI kidney, significantly reducing the pathological features of the kidney and increasing kidney function post IRI.

Department of Zoology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.

For complete study, go to: http://dx.doi.org/10.4236/jbise.2014.78048

Enhanced liver regeneration following acute hepatectomy by low-level laser therapy

Authors: Oron U1, Maltz L, Tuby H, Sorin V, Czerniak A.

Citation: Photomed Laser Surg. 2010 Oct;28(5):675-8. doi: 10.1089/pho.2009.2756. Epub 2010 Oct 9.

The aim of the present study was to investigate the effect of low-level laser therapy (LLLT) on liver regeneration following hepatectomy.

LLLT has been found to modulate various biological processes.

Twelve mature male rats were used. The liver was exposed, and 70% of it was excised. The rats were assigned randomly to two groups: control, non-laser treated, and experimental, laser-treated (diode [Ga-Al-As] laser 804 nm) group. For determination of newly formed blood vessels and proliferating cells, 5-Bromo-2’deoxyuridine (BrdU) was injected intraperitoneally. The rats were sacrificed 2 d post hepatectomy, and histological sections from each liver were processed for analysis of new blood-vessel formation using BrdU immunostaining kit. Mesenchymal stem cells (MSCs) were assessed using c-kit immunostaining. BrdU-labeled cells were counted as for estimation of newly formed hepatic cells.

It was found that the number of proliferating cells (BrdU positive cells) per area in the regenerating regions of the livers were significantly (p < 0.01) 2.6-fold higher in the laser-treated rats than in the control non-laser-treated rats. The density of the newly formed blood vessels and c-kit immunopositive cells in the regenerating area of the laser-treated livers was significantly (p < 0.01) 3.3- and 2.3-fold respectively higher than the control non-laser treated livers.

It is concluded that LLLT following acute hepatectomy most probably stimulates a significant enhancement of liver regeneration conducive to both the formation of new hepatocytes and MSCs and angiogenesis in the regenerating liver.

Author information
1 Department of Zoology, Life Sciences Faculty, Tel-Aviv University, Tel-Aviv, Israel.


Transcranial Laser Stimulation Improves Brain Functions like Attention and Memory – Could it Help with Cluster Headaches or Migraines?


Scientists at the University of Texas-Austin have demonstrated that laser energy stimulates cytochrome oxidase and increases metabolic energy in the brain, leading to improvements in cognitive functions. Clinical studies were done on the prefrontal cortex of rats assessing measurable changes in enzyme levels and activity. Further evaluation of volunteers treated with therapeutic laser highlighted improved memory and reaction time. Laser therapy already has been found to be an effective treatment for relieving the pain of migraines and cluster headaches, but will further studies discover exactly what causes the brain chemicals and nerves to interact and cause such debilitating headaches?

Excerpt from:

Augmentation of cognitive brain functions with transcranial lasers

F. Gonzalez-Lima and Douglas W. Barrett

Discovering that transcranial infrared laser stimulation produces beneficial effects on frontal cortex functions such as sustained attention, working memory, and affective state has been groundbreaking. Transcranial laser stimulation with low-power density (mW/cm2) and high-energy density (J/cm2) monochromatic light in the near-infrared wavelengths modulates brain functions and may produce neurotherapeutic effects in a nondestructive and non-thermal manner (Lampl, 20071; Hashmi et al., 20102). Barrett and Gonzalez-Lima (20133) provided the first controlled study showing that transcranial laser stimulation improves human cognitive and emotional brain functions. …

…LLLT via commercial low-power sources (such as FDA-cleared laser diodes and LEDs) is a highly promising, affordable, non-pharmacological alternative for improving cognitive function. … In 2002, the FDA approved LLLT for pain relief in cases of head and neck pain, arthritis and carpal tunnel syndrome (Fulop et al., 20104). … Even though LLLT has been regarded as safe and received FDA approval for pain treatment, the use of transcranial lasers for cognitive augmentation should be restricted to research until further controlled studies support this application for clinical use. … Healthy volunteers received continuous wave near-infrared light intersecting cytochrome oxidase’s absorption spectrum, delivered to the forehead using a 1064 nm low-power laser diode (also known as “cold laser”), which maximizes tissue penetration due to its long wavelength, and has been used in humans for other indications. …

Transcranial absorption of photon energy by cytochrome oxidase, the terminal enzyme in mitochondrial respiration, is proposed as the bioenergetic mechanism of action of LLLT in the brain. Transcranial LLLT up-regulates cortical cytochrome oxidase and enhances oxidative phosphorylation. LLLT improves prefrontal cortex-related cognitive functions, such as sustained attention, extinction memory, working memory, and affective state. Transcranial infrared stimulation may be used efficaciously to support neuronal mitochondrial respiration as a new non-invasive, cognition-improving intervention in animals and humans. This fascinating new approach should also be able to influence other brain functions depending on the neuroanatomical site stimulated and the stimulation parameters used.

For complete article, go to: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3953713/

Front. Syst. Neurosci., 14 March 2014 | doi: 10.3389/fnsys.2014.00036

1 Lampl, Y. (2007). Laser treatment for stroke. Expert Rev. Neurother. 7, 961–965. doi:10.1586/14737175.7.8.961

2 Hashmi, J. T., Huang, Y. Y., Osmani, B. Z., Sharma, S. K., Naeser, M. A., and Hamblin, M. R. (2010). Role of low-level laser therapy in neurorehabilitation. PM R 2, S292–S305. doi: 10.1016/j.pmrj.2010.10.013

3 Barrett, D.W., Gonzalez-Lima, F. (2013). Transcranial infrared laser stimulation produces beneficial cognitive and emotional effects in humans. Neuroscience. 2013 Jan 29;230:13-23. doi: 10.1016/j.neuroscience.2012.11.016.

4 Fulop, AM, Dhimmer S, Deluca JR, Johanson DD, Lenz RV, Patel KB, Douris PC, Enwemeka CS.(2010). A meta-analysis of the efficacy of laser phototherapy on pain relief. Clin J Pain. 2010 Oct;26(8):729-36. doi: 10.1097/AJP.0b013e3181f09713.

Copyright © 2014 Gonzalez-Lima and Barrett.

Laser Stimulation of Stem Cells in Bone Marrow Could Rebuild Damaged Cells in Yet Another Part of the Body – The Heart


Scientists observed a reduction in scarring of heart tissue after myocardial infarction in rats upon treating a prime source of stem cells, bone marrow in the tibia, with laser energy. They considered the role of circulation of stem cells in the results. This study provides insight into understanding why fibromyalgia and back pain can be relieved with laser therapy by adding a discussion of tissue regeneration through stem cell activation (proof of concept) to the previously understood contribution of increased circulation to healing.

Induction of autologous mesenchymal stem cells in the bone marrow by low-level laser therapy has profound beneficial effects on the infarcted rat heart.

Authors: Tuby H, Maltz L, Oron U.

Citation: Lasers Surg Med. 2011 Jul;43(5):401-9. doi: 10.1002/lsm.21063.


The adult mammalian heart is known to have a very limited regenerative capacity following acute ischemia. In this study we investigated the hypothesis that photobiostimulation of autologous bone-marrow-derived mesenchymal stem cells (MSCs) by low-level laser therapy (LLLT) applied to the bone marrow (BM), may migrate to the infarcted area and thus attenuate the scarring processes following myocardial infarction (MI).

Sprague-Dawley rats underwent experimental MI. LLLT (Ga-Al-As diode laser, power density 10 mW/cm², for 100 seconds) was then applied to the BM of the exposed tibia at different time intervals post-MI (20 minutes and 4 hours). Sham-operated infarcted rats served as control.

Infarct size and ventricular dilatation were significantly reduced (76% and 75%, respectively) in the laser-treated rats 20 minutes post-MI as compared to the control-non-treated rats at 3 weeks post-MI. There was also a significant 25-fold increase in cell density of c-kit+ cells in the infarcted area of the laser-treated rats (20 minutes post-MI) as compared to the non-laser-treated controls.

The application of LLLT to autologous BM of rats post-MI offers a novel approach to induce BM-derived MSCs, which are consequently recruited from the circulation to the infarcted heart and markedly attenuate the scarring process post-MI.

Copyright © 2011 Wiley-Liss, Inc.

Author information
1Department of Zoology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel.
Citation: Lasers Surg Med. 2011 Jul;43(5):401-9. doi: 10.1002/lsm.21063.