Human umbilical cord mesenchymal stem cells to treat spinal cord injury in the early chronic phase: study protocol for a prospective, multicenter, randomized, placebo-controlled, single-blinded clinical trial

Human umbilical cord mesenchymal stem cells(hUC-MSCs)support revascularization,inhibition of inflammation,regulation of apoptosis,and promotion of the release of beneficial factors.Thus,they are regarded as a promising candidate for the treatment of intractable spinal cord injury(SCI).Clinical studies on patients with early chronic SCI(from 2 months to 1 year post-injury),which is clinically common,are rare;therefore,we will conduct a prospective,multicenter,randomized,placebo-controlled,single-blinded clinical trial at the Third Affiliated Hospital of Sun Yat-sen University,West China Hospital of Sichuan University,and Shanghai East Hospital,Tongji University School of Medicine,China.The trial plans to recruit 66 early chronic SCI patients.Eligible patients will undergo randomization at a 2:1 ratio to two arms:the observation group and the control group.Subjects in the observation group will receive four intrathecal transplantations of stem cells,with a dosage of 1×106/kg,at one calendar month intervals.Subjects in the control group will receive intrathecal administrations of 10 mL sterile normal saline in place of the stem cell transplantations.Clinical safety will be assessed by the analysis of adverse events and laboratory tests.The American Spinal Injury Association(ASIA)total score will be the primary efficacy endpoint,and the secondary efficacy outcomes will be the following:ASIA impairment scale,International Association of Neural Restoration-Spinal Cord Injury Functional Rating Scale,muscle tension,electromyogram,cortical motor and cortical sensory evoked potentials,residual urine volume,magnetic resonance imaging–diffusion tensor imaging,T cell subtypes in serum,neurotrophic factors and inflammatory factors in both serum and cerebrospinal fluid.All evaluations will be performed at 1,3,6,and 12 months following the final intrathecal administration.During the entire study procedure,all adverse events will be reported as soon as they are noted.This trial is designed to evaluate the clinical safety and efficacy of subarachnoid transplantation of hUC-MSCs to treat early chronic SCI.Moreover,it will establish whether cytotherapy can ameliorate local hostile microenvironments,promote tracking fiber regeneration,and strengthen spinal conduction ability,thus improving overall motor,sensory,and micturition/defecation function in patients with early chronic SCI.This study was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University,China(approval No.[2018]-02)on March 30,2018,and was registered with ClinicalTrials.gov(registration No.NCT03521323)on April 12,2018.The revised trial protocol(protocol version 4.0)was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University,China(approval No.[2019]-10)on February 25,2019,and released on ClinicalTrials.gov on April 29,2019.

Analysis of correlation between carotid atherosclerotic plaques and serum hs-CRP, Apo-B, ox-LDL and MMP-9 levels in patients with atherosclerotic cerebral infarction

ObjectiveTo analyze the correlation between the levels of serum hypersensitive c-reactive protein(hs-CRP),apolipoprotein-B(Apo-B),oxidized low-density lipoprotein(ox-LDL)and matrix metalloproteinase-9(MMP-9)and carotid arteryplaque(CAP)in patients with atherosclerotic cerebral infarction(ASCI).Methods 125 patients with ASCI diagnosed in the Department of Neurology of Panzhihua Central Hospital from January 2018 to December 2018 were selected as the case group,and 125 healthy volunteers in the same period were selected as the control group.Serum levels of hs-CRP,Apo-B,ox-LDL and MMP-9 were compared between the two groups.Carotid ultrasound was performed in patients with ASCI.The correlation between serum levels of hs-CRP,Apo-B,ox-LDL and MMP-9 and the formation of CAP in patients with ASCI was analyzed by SPSS 23.0 statistics.Results Compared with the control group,the levels of serum hs-CRP,Apo-B,ox-LDL and MMP-9 increased significantly in the case group(P<0.01).The serum levels of hs-CRP,Apo-B,ox-LDL and MMP-9 in patients with CAP were significantly higher than those without CAP in the case group(P<0.01).Multivariate logistic regression analysis showed that serum levels of hs-CRP(OR=4.76,95%CI:2.35-9.18),Apo-B(OR=3.16,95%CI:1.59-7.32),ox-LDL(OR=1.48,95%CI:1.15-2.01)and MMP-9(OR=3.86,95%CI:1.63-9.14)were independent risk factors for CAP formation in patients with ASCI(P<0.05).ConclusionsThe contents of serumhs-CRP,Apo-B,ox-LDL and MMP-9 may reflect the serverity of inflammation and instability of carotid atherosclerotic plaque in ASCI patient.The levels of serum hs-CRP,Apo-B,ox-LDL and MMP-9 in patients with ASCI are significantly increased,which are closely related to the formation of CAP in patients with ASCI,so it can be used as important serum biomarkers for clinical diagnosis of ASCI and CAP formation.