Noninvasive low-level laser therapy for thrombocytopenia

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 g-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, donorindependent modality represents a paradigm shift in the prophylaxis and treatment of thrombocytopenia.

Low-level light treatment ameliorates immune thrombocytopenia

“…Our recent study showed that LLLT bolstered ATP production and mitochondrial biogenesis in MKs18. Whether or not this held true in the presence of anti-CD41 antibody remained unknown.…”

“…Recently, we discovered that 810-nm continuous wave diode laser at 30 J/cm 2 could penetrate into mouse bone marrow noninvasively without incurring any significant heat18. Noninvasive whole body illuminations with the LLLT cured acute thrombocytopenia induced by irradiation, chemotherapeutic drug, or anti-CD41 antibody much faster than sham-light treatment18. We found that LLLT bolstered mitochondrial biogenesis predominantly in polyploid megakaryocytes (MKs), increasing platelet production both in vivo and in vitro 18.…”

“…Noninvasive whole body illuminations with the LLLT cured acute thrombocytopenia induced by irradiation, chemotherapeutic drug, or anti-CD41 antibody much faster than sham-light treatment18. We found that LLLT bolstered mitochondrial biogenesis predominantly in polyploid megakaryocytes (MKs), increasing platelet production both in vivo and in vitro 18. In the current study, we apply an array of light-emitting diodes (LEDs), instead of diode laser, to two passive ITP mouse models to gain similar results.…”

“…Several investigators, including us, have shown that low-level light treatment (LLLT) modulates ATP production, reactive oxygen species (ROS) formation, apoptosis, cellular metabolic process, and signaling transduction pathways secondarily to more sufficient function of mitochondria under various conditions of stress151617. Recently, we discovered that 810-nm continuous wave diode laser at 30 J/cm 2 could penetrate into mouse bone marrow noninvasively without incurring any significant heat18. Noninvasive whole body illuminations with the LLLT cured acute thrombocytopenia induced by irradiation, chemotherapeutic drug, or anti-CD41 antibody much faster than sham-light treatment18.…”

Low-level light treatment ameliorates immune thrombocytopenia

“…Several investigators, including us, have shown that low-level light treatment (LLLT) modulates ATP production, reactive oxygen species (ROS) formation, apoptosis, cellular metabolic process, and signaling transduction pathways secondarily Scientific RepoRts | 6:38238 | DOI: 10.1038/srep38238 to more sufficient function of mitochondria under various conditions of stress [15][16][17] . Recently, we discovered that 810-nm continuous wave diode laser at 30 J/cm 2 could penetrate into mouse bone marrow noninvasively without incurring any significant heat 18 . Noninvasive whole body illuminations with the LLLT cured acute thrombocytopenia induced by irradiation, chemotherapeutic drug, or anti-CD41 antibody much faster than sham-light treatment 18 .…”