Noninvasive low-level laser therapy for thrombocytopenia
Authors: Peiyu Li
Mei X Wu
Tingting Dong
Qi Zhang
Journal: Science Translational Medicine (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Thrombocytopenia; platelet transfusions; near-infrared laser; acute thrombocytopenia; low-level laser (LLL)
Affiliations: Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA. Department of Dermatology, Harvard Medical School, Boston, MA 02114, USA., Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA. Department of Dermatology, Harvard Medical School, Boston, MA 02114, USA. Affiliated faculty member of the Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02115, USA. .

Abstract:  Thrombocytopenia is a common hematologic disorder that is managed primarily by platelet transfusions. We report here that noninvasive whole-body illumination with a special near-infrared laser cures acute thrombocytopenia triggered by Œ≥-irradiation within 2 weeks in mice, as opposed to a 5-week recovery time required in controls. The low-level laser (LLL) also greatly accelerated platelet regeneration in the presence of anti-CD41 antibody that binds and depletes platelets, and prevented a severe drop in platelet count caused by a common chemotherapeutic drug. Mechanistically, LLL stimulated mitochondrial biogenesis specifically in megakaryocytes owing to polyploidy of the cells. LLL also protected megakaryocytes from mitochondrial injury and apoptosis under stress. The multifaceted effects of LLL on mitochondria bolstered megakaryocyte maturation; facilitated elongation, branching, and formation of proplatelets; and doubled the number of platelets generated from individual megakaryocytes in mice. LLL-mediated platelet biogenesis depended on megakaryopoiesis and was inversely correlated with platelet counts, which kept platelet biogenesis in check and effectively averted thrombosis even after repeated uses, in sharp contrast to all current agents that stimulate the differentiation of megakaryocyte progenitors from hematopoietic stem cells independently of platelet counts. This safe, drug-free, donor-independent modality represents a paradigm shift in the prophylaxis and treatment of thrombocytopenia. 

Retracted: No

PubPeer comments:
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 Another puzzling aspect of this paper is the experiment shown in Figure 7, where cultured human megakaryocyte progenitors and developing megakaryocytes are treated with low-level laser therapy for several days, with a readout at 15 days being the numbers of platelets produced. It is well established in the literature that platelet production by megakaryocytes requires near-physiological conditions (flow, turbulence, endothelium, etc.) and does not occur in static culture to any meaningful extent. Indeed there are many efforts underway to establish systems where platelet production is sufficient ex vivo to generate transfusable cells. Yet these authors claim they generated several hundred platelets per progenitor. That does not seem possible, and the authors do not present evidence regarding the morphology of the  platelets they claim to have generated. Can they provide more insights into what was actually counted in this experiment? ,