The effect of platelet infusion on the repair of bone marrow hematopoietic niche damage in mice induced by (60)Co radiation and hematopoietic reconstruction after bone marrow transplantation / 中华血液学杂志

Objective: To observe the effect of platelets on hematopoietic stem cell (HSCs) implantation in mice with radiation-induced bone marrow injury and bone marrow transplantation models. Methods: ①Male C57BL/6 mice were divided into a single irradiation group and a radiation infusion group after receiving (60)Co semimyeloablative irradiation for 18-10 weeks. The irradiation infusion group received 1×10(8) platelets expressing GFP fluorescent protein. ② The allogeneic bone marrow transplantation model was established. The experimental groups included the simple transplantation group (BMT) and the transplantation infusion group (BMT+PLT). The BMT group was infused through the tail vein only 5 × 10(6) bone marrow cells, the BMT+PLT group needs to be infused with bone marrow cells at the same time 1× 10(8) platelets. ③ Test indicators included peripheral blood cell and bone marrow cell counts, flow cytometry to detect the proportion of hematopoietic stem cell (HSC) and hematopoietic progenitor cells, bone marrow cell proliferation and apoptosis, and pathological observation of vascular niche damage and repair. Results: ①On the 3rd, 7th, 14(th), and 21st days after irradiation, the bone marrow cell count of the infusion group was higher than that in the single irradiation group (P<0.05), and the peripheral blood cell count was also higher. A statistically significant difference was found between the white blood cell count on the 21st day and the platelet count on the 7th day (P<0.05). In the observation cycle, the percentage of bone marrow cell proliferation in the infusion group was higher, while the percentage of apoptosis was lower. ② The results of bone tissue immunofluorescence after irradiation showed that the continuity of hematopoietic niche with red fluorescence was better in the irradiation infusion group. ③The chimerism percentage in the BMT+PLT group was always higher than that in the BMT group after transplantation.④ The BMT+PLT group had higher bone marrow cell count and percentage of bone marrow cell proliferation on the 7th and 28th day after transplantation than that in the BMT group, and the percentage of bone marrow cell apoptosis on the 14th day was lower than that in the BMT group (P<0.05). After the 14th day, the percentage of stem progenitor cells in the bone marrow cells of mice was higher than that in the BMT group (P<0.05). ⑤The immunohistochemical results of bone marrow tissue showed that the continuity of vascular endothelium in the BMT+PLT group was better than that in the BMT group. Conclusion: Platelet transfusion can alleviate the injury of vascular niche, promotes HSC homing, and is beneficial to hematopoietic reconstruction.

Relationship between NLRP1 and Liver Dysfunction Following Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of NLRP1 on the liver dysfunction following allogeneic hematopoietic stem cell transplantation(allo-HSCT).</p><p><b>METHODS</b>The mouse model of allo-HSCT was established by using C57BL/6 and NLRP mice were used as the recipients: BABL/c mice were used as donors). The chimera rates of donor's bone marrow cells were assayed by flow cytometry. ALT and AST levels were measured by automatic biochemical analyzer. Western blot was used to detect the expressions of NLRP1, the precursor of Caspase-1 and its active segment p20,IL-1β,IL-18 and MPO in livers.</p><p><b>RESULTS</b>The chimera rate was over 96% on the day 14 after allo-HSCT, and showed that the hematopoietic stem cells of donors had been transplanted into recipients. ALT and AST levels were increased from (173.9±12.39)U/L and (283.7±28.00)U/L on day 7 to (3902±1745)U/L and (5316±924)U/L on the day 14 and decreased to (3153±564.4) U/L and (4350±957.7) U/L on the day 28, respectively. Western blot showed that the expression of NLRP1 was increased after allo-HSCT, which displayed a similar trend with the changes of ALT and AST. When knocking out NLRP1, the contents of ALT and AST in the knocked group were significantly decreased in comparison with the group without knocking out. And the expression levels of NLRP1 related inflammatory proteins, precursor of Caspase-1,p20,Mature-IL-1β,Mature-IL-18 and MPO were lower than those in groups without knocking out NLRP1 gene.</p><p><b>CONCLUSION</b>Allo-HSCT can cause the damage of liver function and increase the expression of NLRP1, while knocking out NLRP1 can reduce the damage of liver function, so NLRP1 may be one of the important factors leading to liver dysfunction.</p>

Advances of Studies on Platelet GPVI as Antithrombotic Target -Review / 中国实验血液学杂志

Platelet activation is a crucial step in both physiological hemostasis and pathological thrombosis, which is an important mean to prevent and treat thrombotic diseases by inhibition of platelet activation. The current clinical antithrombotic therapy showed a high efficiency, but at risk of bleeding. Platelet glycoprotein VI (GPVI) is a platelet-specific receptor and its binding with collagen is critical for platelet activation. GPVI antagonists were shown to effectively inhibit thrombosis and inflammation without influence on normal hemostasis. As a novel target for antithrombotic therapy, it ideally combines efficacy with safety. This review summarizes the recent advances of studies on GPVI structure, function and its role in hemostasis, thrombosis, and anti-GPVI agents. The potential clinical strategies of antiplatelet drugs targeting GPVI are discussed so as to provide a reliable regimen for thrombotic diseases.

Research Progress on Roles of Platelets in Tissue Repair -Review / 中国实验血液学杂志

Platelets are known to play a critical role in thrombosis and hemostasis. However, recent studies demonstrated that beyond their role in thrombosis and hemostasis, platelets are also involved in the regulation of tissue repair and regeneration. Increasing number of studies on the roles of platelets in tissue repair showed that various growth factors, chemokines as well as cytokines secreted from activated platelets regulate injured tissue repair and regeneration with the main mechanisms being through regulation of cell migration, proliferation, and angiogenesis, cell apoptosis and survival. Deeply understanding the molecular mechanism of tissue repair induced by platelets might promote their application in clinic. This review discusses the structure and function of platelets, the mechanism of platelet-induced tissue repair as well as clinical application of platelets.