Mechanisms of Laser Induced Hair Regrowth (In other words, how LLLT fights Hair Loss!)

Special thanks goes to chore boy from Regrowth for bringing this to our attention.

http://​hairrejuvenator.com/​pdf/​Induced_​Laser_​Hair_​regrowth_​Harvard​_Medical​.pdf

Here is one of the more important parts of the article that I have included first

"A Japanese group reported on the use of Super Lizer (a linear polarized light source providing 1.8 W of 600 to 1600nm light) to treat alopecia areata. Three minute sessions every one or two weeks produced significant hair growth compared to non-treated lesions in 47% of patients."

"IncreasedRNA and protein synthesis was demonstrated after 5J/cm2. Pastore et al found increased activity ofcytochrome c oxidase and an increase in polarograph-ically measured oxygen uptake after 2 J/cm2of HeNe.A major stimulation in the proton pumping activity,about 55% increase of H+/e- ratio was found in illu-minated mitochondria. Yu et al used a 660 nm laser ata power density of 10 mW/cm2and showed increasedoxygen consumption (0.6 J/cm2and 1.2 J/cm2),increased phosphate potential, and energy charge (1.8J/cm2and 2.4 J/cm2) and enhanced activities ofNADH: ubiquinone oxidoreductase, ubiquinol: ferricy-tochrome C oxidoreductase and ferrocytochrome C:oxygen oxidoreductase (0.6 J/cm2, 1.2 J/cm2, 2.4 J/cm2and 4.8 J/cm2)."

"Another report found a greater effect of LLLT in stimulating wound healing in malnourished compared to normally fed rats."

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LLLT for Hair Regrowth

Since the first pioneering publication of Mesterreported stimulation of hair growth in mice, there havebeen virtually no follow-up studies on LLLT stimula-tion for hair growth in animal models. Mester’s studyinvolved delivering 1 J of pulsed light (one millisecondpulse duration) into a 1 cm2spot from a ruby laser at694 nm to the depilated abdominal area of black C57and white Balb/c mice every week for up to 11 weeks.Before each successive treatment the skin was againdepilated. Increased hair growth in the irradiated spotwas observed in all black animals between the fifthand seventh treatment. This reaction continued to theninth treatment and it was characteristic of the hairgrowth intensity that in places which were completelybare at the time of the respective irradiation, hairgrowth as dense as on other body parts was observedonly four to six days after the irradiation.On the other hand, it was found after the ninthirradiation that hair growth stopped in the irradiatedlocations only. Instead, a peripheral, ring-shaped hairgrowth was observed around the irradiated area. Thisring-shaped hair growth first appeared on the animalwhich the central growth stimulation was firstobserved. The peripheral growth appeared in all treat-ed black mice between the seventh and ninth irradia-tion with the intensity varying from mouse to mouse.In white mice no effect on hair growth was detected upto the eighth irradiation. The central growth describedfor black mice only began to form after the eighth irra-diation. Further irradiation caused the hair growth asdescribed in some of the mice, but the peripheral hairgrowth characteristic of the second phase was alreadyappearing in some as well. The hair growth of the con-trol animals developed as follows: The depilated skingrew hair slowly and diffusely. However, on half of thecontrol animals (both among black and white mice), nofurther hair growth whatsoever was observed. At thesame time, a diffuse hair growth appeared on someanimals, but in other animals an uncharacteristic,sometimes diagonal strip appeared.Despite the fact that LLLT devices are widely mar-keted and used for hair regrowth, there have been onlya few written reports containing some observations ofLLLT-induced hair growth in patients, and ameliora-tion or treatment of any type of alopecia. A Japanesegroup reported on the use of Super Lizer (a linearpolarized light source providing 1.8 W of 600 to 1600nm light) to treat alopecia areata. Three minute ses-sions every one or two weeks produced significant hairgrowth compared to non-treated lesions in 47% ofpatients. A Spanish group has reported on the use ofHeNe laser for both alopecia androgenic and areata. A report from Finland compared three different lightsources used for male pattern baldness (HeNe laser,InGaAl diode laser at 670 nm and non-coherent 635nm LED and measured blood flow in the scalp.Recent work has uncovered some biological mecha-nisms involved in the regulation of hair growth thatcould be good candidates to explain the stimulatingeffects of LLLT. Peters et al found that Nerve GrowthFactor (NGF) promotes proliferation via its high affinityreceptor (TrkA), and identified NGF and p75 as impor-tant hair growth terminators. By rtPCR we found, thatNGF/proNGF mRNA levels peak during early anagen inmurine back skin while NGF/proNGF protein levelspeak during catagen, indicating high turnover in earlyanagen and protein accumulation in catagen. Byimmunohistochemistry, NGF and TrkA were found inthe proliferating compartments of the epidermis andhair follicle throughout the cycle. Commercial 7S NGF,which contains both NGF and proNGF, promotes ana-gen development in organ cultured early anagen mouseskin, while it promotes catagen development in late ana-gen skin. Therefore the data suggests an anagen pro-moting/supporting role for NGF/TrkA.Another report from this group studied the expres-sion and function of p75 neurotrophin receptor(p75NTR), which is implicated in apoptosis control inspontaneous catagen development in murine skin.They found that p75NTR alone was strongly expressedin TUNEL+/Bcl2- keratinocytes of the regressing outerroot sheath, but both p75NTR and TrkB and/or TrkCwere expressed by the non-regressing TUNEL-/Bcl2+secondary hair germ keratinocytes. There was signifi-cant catagen retardation in p75NTR knockout mice ascompared to wild-type controls. Instead, transgenicmice over expressing NGF (promoter: K14) showedsubstantial acceleration of catagen.Schwartz et al reported in 2002 that helium/neonlaser irradiation (3 J/cm2) augmented the level of NGFmRNA fivefold and increased NGF release to the medi-um of myotubes cultured in vitro. This correlated witha transient elevation of intracellular calcium in themyotubes. Yu and co-workers found a significantincrease in nerve growth factor release from culturedhuman keratinocytes. Therefore it is postulated thatLLLT may influence hair regrowth via theNGF/p75NTR signaling system.Zcharia and colleagues identified the endoglycosi-dase, heparanase, as an important regulator of murinehair growth. Degradation of the extracellular matrix bar-rier formed by heparan sulfate by heparanase enablescell movement through extracellular barriers and releas-es growth factors from extracellular matrix depots, mak-ing them bio-available. This allows follicular stem cellprogeny migration and reconstitution of the lower part ofthe follicle, which is a prerequisite for hair shaft forma-tion. Heparanase contributed to the ability of the bulge-derived keratinocytes to migrate through the extracellu-lar matrix barrier in vitro. In heparanase over express-ing transgenic mice, increased levels of heparanaseenhanced active hair growth and enabled faster hairrecovery after chemotherapy induced alopecia.Thymosin beta4 (TB4) is a 43-amino acid polypep-tide, an important mediator of cell migration and dif-ferentiation, also promotes angiogenesis and woundhealing. Philp et al reported that TB4 stimulated hairgrowth in normal rats and mice. A specific subset ofhair follicular keratinocytes in mouse skin expressedTB4 in a highly coordinated manner during the hairgrowth cycle. These keratinocytes originated in thehair follicle bulge region, a niche for skin stem cells.Rat vibrissa follicle clonogenic keratinocytes, closelyrelated, if not identical, to the bulge residing stem cells,were isolated and their migration and differentiationincreased in the presence of nanomolar concentrationsof TB4. Expression and secretion of the extracellularmatrix-degrading enzyme matrix metalloproteinase-2was increased by TB4. Thus, TB4 accelerated hairgrowth, in part, due to its effect on critical events in theactive phase of the hair follicle cycle, including pro-moting the migration of stem cells and their immediateprogeny to the base of the follicle, differentiation andextracellular matrix remodeling.A recent report identified the transforminggrowth factor-beta family member, activin, as apotent regulator of skin morphogenesis, repair andhair growth. Mice over expressing the secretedactivin antagonist follistatin, however, have reducedhair growth. Mice expressing a dominant negativeactivin receptor IB mutant (dnActRIB) in ker-atinocytes had unaltered architecture of adult skin,but delays were observed in postnatal pelage hair fol-licle morphogenesis and in the first catagen-telogentransformation of hair follicles.As yet there are no reports of LLLT affectingheparanase, TB4, or activin expression levels in tissueculture or in mouse skin, but these molecules are goodcandidates for further study to explain the hair growthinduction by LLLT.IThe research and production of this paper weremade possible by a grant from Laser Hair Therapy ofNorth America, LLC. 21 Madison Plaza, Suite 129 •Madison, NJ 07940 USA Tel: 1-877-917-4247 • Fax: 1-973-539-7445 www.lhtna.com. For the full length ver-sion of this paper with bibliography, please contactLaser Hair Therapy of North America, LLC directly.