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 γ-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.