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.
Wyss 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.
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