Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells a...Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.展开更多
Glanzmann’s thrombasthenia(GT)is an inherited autosomal recessive bleeding disorder,resulting from mutations in the ITGA2B and ITGB3 genes,that lead to a defect in the platelet membrane integrinαIIbβ3.[1]As integri...Glanzmann’s thrombasthenia(GT)is an inherited autosomal recessive bleeding disorder,resulting from mutations in the ITGA2B and ITGB3 genes,that lead to a defect in the platelet membrane integrinαIIbβ3.[1]As integrinαIIbβ3 plays an important role in thrombus formation,the clinical manifestation of GT includes bleeding(mostly mucocutaneous)and purpura.For this reason,patients with GT are typically thought to be unlikely to suffer from thromboembolic incidents.Antithrombin is an anticoagulant that inhibits thrombin and is activated factor X and other serine proteases in the coagulation cascade.[2]Antithrombin deficiency is an autosomal dominant hereditary disease with an approximate prevalence of 1/500 in the overall population.[3]In contrast to the hemorrhagic tendency of GT,patients with antithrombin deficiency are at increased risk of thromboembolism,especially in the venous system.Herein,we describe a rare case of GT and antithrombin deficiency coexisting in a single patient.Rivaroxaban was used for the treatment of pulmonary embolism(PE)and deep vein thrombosis(DVT).展开更多
基金supported by the Stem Cell and Translation National Key Project,No.2016YFA0101403(to ZC)the National Natural Science Foundation of China,Nos.82171250 and 81973351(to ZC)+6 种基金the Natural Science Foundation of Beijing,No.5142005(to ZC)Beijing Talents Foundation,No.2017000021223TD03(to ZC)Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan,No.CIT&TCD20180333(to ZC)Beijing Municipal Health Commission Fund,No.PXM2020_026283_000005(to ZC)Beijing One Hundred,Thousand,and Ten Thousand Talents Fund,No.2018A03(to ZC)the Royal Society-Newton Advanced Fellowship,No.NA150482(to ZC)the National Natural Science Foundation of China for Young Scientists,No.31900740(to SL)。
文摘Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.
文摘Glanzmann’s thrombasthenia(GT)is an inherited autosomal recessive bleeding disorder,resulting from mutations in the ITGA2B and ITGB3 genes,that lead to a defect in the platelet membrane integrinαIIbβ3.[1]As integrinαIIbβ3 plays an important role in thrombus formation,the clinical manifestation of GT includes bleeding(mostly mucocutaneous)and purpura.For this reason,patients with GT are typically thought to be unlikely to suffer from thromboembolic incidents.Antithrombin is an anticoagulant that inhibits thrombin and is activated factor X and other serine proteases in the coagulation cascade.[2]Antithrombin deficiency is an autosomal dominant hereditary disease with an approximate prevalence of 1/500 in the overall population.[3]In contrast to the hemorrhagic tendency of GT,patients with antithrombin deficiency are at increased risk of thromboembolism,especially in the venous system.Herein,we describe a rare case of GT and antithrombin deficiency coexisting in a single patient.Rivaroxaban was used for the treatment of pulmonary embolism(PE)and deep vein thrombosis(DVT).
