Abstract
D
Although the progress with backward stem cell fate has been laudable, indeed with recognition of Nobel prizes for the discoverers, the forward directed differentiation to an architectural and physiologically functional form has yet to be fully realized. 2 These efforts have not lacked enthusiasm nor motivation; rigorous efforts have been made with a wide range of candidates from regulatory biomolecules to exquisitely designed small molecules. Many of these approaches have been met with varying degrees of success, but are yet to develop into a clinically effective regenerative therapy. Clearly much effort, along with perhaps a different perspective, is warranted.
Biophysical modalities such as ultrasounds, radiofrequency, and light treatments have all been tried many times but are largely relegated to alternative therapies. 3 The subtle, rapid (sub-second), and broadly potent biophysical nature of these treatments is not only opening new vistas in our understanding of biological systems, but also holds much promise as innovative, noninvasive therapies. This special issue in the journal of Photomedicine and Laser Surgery focuses on low-dose biophotonics therapy, in particular, photobiomodulation (PBM) therapy and stem cells for regenerative clinical applications, which is one such alternative approach. This issue brings together a group of articles that showcase the tremendous excitement and broad therapeutic potential of PBM regenerative therapy.
PBM treatments have been used by a large number of biomedical researchers and clinical practitioners who speak of both its enormous impact and the deluge of scientific literature causing confusion that raises concerns about treatment safety and efficacy. Indeed, the extrapolation of “light” as a universal entity to “light treatments” as a cure-all panacea is disingenuous. There are clearly discrete biological processes and disease ailments that have responded well to PBM therapy. Ongoing research is attempting to make these clinical outcomes consistent and reproducible to enable its development as a mainstream therapy.
As a PBM clinical researcher working in the trenches, it has always been fascinating to observe the three major audience responses in our various forums. The first response is from folks who are hearing about this treatment for the very first time—“This cannot be true!” “You got to be kidding—light can do that?” “Astonishing, we must learn more…”. These responses are somewhat surprisingly given their ready acceptance of the Hollywood version of this treatment from the most touted device in our field, the Star Trek Tricoder, to the light healing device in the movie Oblivion. The second usual response when one hears about PBM therapy is from the practitioners or beneficiaries who have experienced the treatment first hand. They are most interested in asking—“What is your best wavelength?” “What is your dose?” “How long or often should I treat?” “Do LEDs work as well as Lasers?” The third response is from the skeptics who go—“No way, this is pseudoscience”… “Not possible.” This is usually despite being presented with sound scientific evidence! Perhaps their cynicism stems from their classical biological or pharmacological training; they cannot fathom how such low doses of photonic energies—almost ambient light doses—are capable of such therapeutic benefits. It is a little perplexing that the very vision enabling them to view these pieces of evidence is fundamentally a similar process—the ability of visible light to modulate the conformation of the retinal pigments (rhodopsin) that initiates downstream biological signaling and neuroperception. Moreover, there is a growing body of evidence that nonvisual phototransduction has key roles in various physiological processes such as circadian rhythms, endocrine-hormonal regulation, and even behavioral patterns. 4
Although many of these audience questions need to be carefully addressed in helping move the PBM clinical therapy field forward, it is also surprising that there seems to be a lack of interest from mainstream academic funding agencies in promoting sorely needed research in this field. Nonetheless, there are growing efforts on standardization of reporting PBM treatment in clinical delivery parameters. 5 A critical variable among these is the practical, clinical delivery of biophotonics energy, especially with deep-seated pathologies such as in the abdomen or knee joint, or within the brain. Although these approaches will allow accurate configuration of our PBM devices, a key question that still remains is what type (wavelength, amplitude, and frequency) and how much (irradiance, time, fluence = dose) light is necessary to evoke a specific biological therapeutic response in a given pathophysiological (context) scenario? 6 Clearly, much work is still needed. However, this does not imply that the clinical PBM treatments should stop until all the mechanisms are figured out. After all, within the Hippocratic Oath to do no harm, we must utilize all possible means (with rigorous attention to safety) to benefit our patients today.
To end on an optimistic note, light appears to present the ultimate frontier in life as we know it, from cosmology, physics, and chemistry. 7 Clinical medicine seems to be poised to harness the tremendous potential of biophotonics, largely due to the exquisite temporal and spatial control it offers to harness biological regulation. Indeed, light may just be the uniquely different approach that could lead to dramatic changes in personalized, regenerative precision medicine landscape.