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Implementation of laser therapy in practice                 181


                   usually from the wing of the ilium, or we take a piece   proliferation. Also, irradiating cultures every day or
                   of fat, generally from the inguinal area or falciform   every other day for a certain period gave better results
                   ligament.                                         than a single exposure.
                     When stem cells are cultivated, which usually takes   Osteoarthritis and tendon and ligament injuries are
                   about 20 days, one of the key questions is how to make   the most common conditions in which stem cells are
                   them proliferate more; there is a critical number of cells   employed in clinical settings, [471, 472]  but very promis-
                   that need to be implanted/administered to achieve an   ing results are being reported in inflammatory condi-
                   effect (several hundred thousand to several millions,   tions of the nervous system, [473]  spinal cord injuries, [474]
                   depending on the case). After that, survival and success   inflammatory bowel disease, [475]  and others. To answer
                   depend on the transplantation method – either in sus-  the question about increased survival of stem cells and
                   pension or with different scaffolds, with or without   their clinical effect when combining them with apply-
                   growth factors – and recipient environment, both in   ing LT to the animal, these are some of the fields in
                   terms of the microenvironment and considering the   which the combination has been investigated with suc-
                   mechanical forces the area is subjected to.       cessful results in experimental models.
                     Having said this, the following questions arise.
                                                                     •  Bone repair, and in particular in maxillofacial
                   •  Before the tissue is harvested, could LT improve   reconstruction: for example, LT has been used in
                      local conditions for a more successful harvest?   the search for strategies to close large alveolar clefts
                   •  Can we encourage cells to survive and proliferate   in patients with cleft lips and palates. When dental
                      more while being cultured in vitro?               pulp stem cells are treated in vitro with LT, they
                   •  Could preconditioning with LT improve local con-  show enhanced osteogenic potential. [476]
                      ditions in the area that will receive the stem cells?  •  Myocardial infarction is a common cause of disease
                   •  Would LT after implanting stem cells improve their   and death in humans, and stem cells are also being
                      viability and proliferation? Would that have a clini-  investigated in this field to help with recovery of
                      cal effect?                                       the infarcted heart. In one particular study, treat-
                                                                        ing stem cells with LT increased  their survival,
                     In vitro experiments show LT increases human       proliferation, and homing, which manifested as a
                   adipose  stem cell viability  and proliferation, [465]  and   decrease in the infarct size and cell death and there-
                   the same results have been found in bone marrow      fore enhanced cardiac function. [477]
                   mesenchymal stem cells: greater osteogenic poten-  •  Neurological injury: in a model of nerve crush
                   tial  after  LT, plus  an  increase in  extracellular  levels   injury, the combination of LT and stem cell implant
                   of TGF-β, IGF-I, and ALP. [466]  While growth factors   provided better functional recovery than either
                   increase, LT suppresses transcription factor NF-κB (via   therapy alone. [372]
                   an increase in cAMP), and therefore the expression of   •  Hindlimb ischemia: treating the implanted stem
                   IL-1β, IL-6, and IL-8; this also happens even when stem   cells with LT increased the angiogenesis, tissue
                   cells are previously challenged with lipopolysaccha-  regeneration,  and  functional  recovery  in  a mouse
                   ride to experimentally induce inflammation. [467]  These   model of hindlimb ischemia. [478]
                   molecular changes lead to increased survival and prolif-
                   eration. But stem cells don’t just grow more and faster:   Again, we know laser works. But these studies are
                   they differentiate more into neurons and osteoblasts   actually in vitro and experimental. We can’t just assume
                   when treated with laser, [468]  and all of these effects lead   those laser-preconditioned cells that proliferate and
                   to improved tissue healing in experimental animals. [469]    work better in experimental animals will behave the
                   The optimal parameters to increase proliferation can   same in clinical cases of a different species, and we still
                   be different from those to achieve maximal differentia-  have questions about the best way to stimulate cells
                   tion. A review of 73 publications concluded that both   both in cultures and once implanted. The methodologi-
                   dose and power density influenced the results, and the   cal heterogeneity of the studies does not help to deter-
                   maximum proliferation was achieved with 0.5 to 4 J/  mine which are the best parameters and the effect in
                   cm 2[470] . Power densities ranged from 2 to 125 mW/  clinical patients. [479]  Clinical research will provide more
                   cm , with higher values in that range leading to more   answers to those key questions in the next years. My
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         REDONDO PRINT (4-COL BLEED).indd   181                                                                        08/08/2019   09:49
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