Stem cell transplantation can promote functional restoration following acute spinal cord injury （injury time 〈 3 months）, but the safety and long-term efficacy of this treatment need further exploration. In this st...Stem cell transplantation can promote functional restoration following acute spinal cord injury （injury time 〈 3 months）, but the safety and long-term efficacy of this treatment need further exploration. In this study, 25 patients with traumatic spinal cord injury （injury time 〉 6 months） were treated with human umbilical cord blood stem cells via intravenous and intrathecal injection. The follow-up period was 12 months after transplantation. Results found that autonomic nerve functions were restored and the latent period of somatosensory evoked potentials was reduced. There were no severe adverse reactions in patients following stem cell transplantation. These experimental findings suggest that the transplantation of human umbilical cord blood stem cells is a safe and effective treatment for patients with traumatic spinal cord injury展开更多
METRNL is a recently identified secreted protein with emerging functions.This study is to find major cellular source of circulating METRNL and to determine METRNL novel function.Here,we show METRNL is abundant in huma...METRNL is a recently identified secreted protein with emerging functions.This study is to find major cellular source of circulating METRNL and to determine METRNL novel function.Here,we show METRNL is abundant in human and mouse vascular endothelium and released by endothelial cells using endoplasmic reticulum-Golgi apparatus pathway.By creating endothelial cell-specific Metrnl knockout mice,combined with bone marrow transplantation to produce bone marrow-specific deletion of Metrnl,we demonstrate that most of circulating METRNL(approximately 75%)originates from the endothelial cells.Both endothelial and circulating METRNL decrease in atherosclerosis mice and patients.By generating endothelial cell-specific Metrnl knockout in apolipoprotein E-deficient mice,combined with bone marrow-specific deletion of Metrnl in apolipoprotein E-deficient mice,we further demonstrate that endothelial METRNL deficiency accelerates atherosclerosis.Mechanically,endothelial METRNL deficiency causes vascular endothelial dysfunction including vasodilation impairment via reducing eNOS phosphorylation at Ser1177 and inflammation activation via enhancing NFκB pathway,which promotes the susceptibility of atherosclerosis.Exogenous METRNL rescues METRNL deficiency induced endothelial dysfunction.These findings reveal that METRNL is a new endothelial substance not only determining the circulating METRNL level but also regulating endothelial function for vascular health and disease.METRNL is a therapeutic target against endothelial dysfunction and atherosclerosis.展开更多
文摘Stem cell transplantation can promote functional restoration following acute spinal cord injury （injury time 〈 3 months）, but the safety and long-term efficacy of this treatment need further exploration. In this study, 25 patients with traumatic spinal cord injury （injury time 〉 6 months） were treated with human umbilical cord blood stem cells via intravenous and intrathecal injection. The follow-up period was 12 months after transplantation. Results found that autonomic nerve functions were restored and the latent period of somatosensory evoked potentials was reduced. There were no severe adverse reactions in patients following stem cell transplantation. These experimental findings suggest that the transplantation of human umbilical cord blood stem cells is a safe and effective treatment for patients with traumatic spinal cord injury
基金supported by grants from the National Natural Science Foundation of China Major Project(Nos.81730098 and 82030110)National Natural Science Foundation of China Young Program(No.82104165)+2 种基金Shanghai Science and Technology Commission Project(No.201409004600,China)Shanghai Sailing Program(No.21YF1457600,China)Medical Innovation Project(Nos.16CXZ009,16QNP087 and 2018-CGPZ-A03,China)。
文摘METRNL is a recently identified secreted protein with emerging functions.This study is to find major cellular source of circulating METRNL and to determine METRNL novel function.Here,we show METRNL is abundant in human and mouse vascular endothelium and released by endothelial cells using endoplasmic reticulum-Golgi apparatus pathway.By creating endothelial cell-specific Metrnl knockout mice,combined with bone marrow transplantation to produce bone marrow-specific deletion of Metrnl,we demonstrate that most of circulating METRNL(approximately 75%)originates from the endothelial cells.Both endothelial and circulating METRNL decrease in atherosclerosis mice and patients.By generating endothelial cell-specific Metrnl knockout in apolipoprotein E-deficient mice,combined with bone marrow-specific deletion of Metrnl in apolipoprotein E-deficient mice,we further demonstrate that endothelial METRNL deficiency accelerates atherosclerosis.Mechanically,endothelial METRNL deficiency causes vascular endothelial dysfunction including vasodilation impairment via reducing eNOS phosphorylation at Ser1177 and inflammation activation via enhancing NFκB pathway,which promotes the susceptibility of atherosclerosis.Exogenous METRNL rescues METRNL deficiency induced endothelial dysfunction.These findings reveal that METRNL is a new endothelial substance not only determining the circulating METRNL level but also regulating endothelial function for vascular health and disease.METRNL is a therapeutic target against endothelial dysfunction and atherosclerosis.
