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Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

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Neural Regeneration Research 2025年第5期20卷 1467-1482页

作者： Wenrui Qu Xiangbing Wu Wei Wu Ying Wang Yan Sun Lingxiao Deng Melissa Walker Chen Chen Heqiao Dai Qi Han Ying Ding Yongzhi Xia George Smith Rui Li Nai-Kui Liu Xiao-Ming Xu Spinal Cord and Brain Injury Research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA department of Hand surgery the Second Hospital of Jilin UniversityChangchunJilin ProvinceChina Shriners Hospitals pediatric Research Center Temple University School of MedicinePhiladelphiaPAUSA department of Anatomy&cell biology Indiana University School of MedicineIndianapolisINUSA

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal *** we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord *** report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal *** Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder ***,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord *** findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

关键词： axonal regrowth bladder function chondroitinase ABC functional recovery glial scar lentivirus migration Schwann cell spinal cord injury transplantation

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Single-cell omics: experimental workflow, data analyses and applications

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Science China Life Sciences 2025年第1期68卷 5-102页

作者： Fengying Sun Haoyan Li Dongqing Sun Shaliu Fu Lei Gu Xin Shao Qinqin Wang Xin Dong Bin Duan Feiyang Xing Jun Wu Minmin Xiao Fangqing Zhao Jing-Dong J.Han Qi Liu Xiaohui Fan Chen Li Chenfei Wang Tieliu Shi department of Clinical laboratory the Affiliated Wuhu Hospital of East China Normal University (The Second People's Hospital of Wuhu City) Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang University Key laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Tongji University) Ministry of EducationOrthopaedic DepartmentTongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Frontier Science Center for stem cells School of Life Sciences and TechnologyTongji University Translational Medical Center for stem cell Therapy and Institute for Regenerative Medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Research Institute of Intelligent Computing Zhejiang Lab Shanghai Research Institute for Intelligent Autonomous Systems Center for Single-cell Omics School of Public HealthShanghai Jiao Tong University School of Medicine National Key laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River DeltaZhejiang University Center for Bioinformatics and Computational biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal University Beijing Institutes of Life Science Chinese Academy of Sciences Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative Biology (CQB)Peking University Zhejiang Key laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women's HospitalZhejiang University School of Medicine Key laboratory of Advanced Theory and Application in Statistics and Data Science-MOE School of StatisticsEast China Normal University

cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular features. Our exploration of how the genomes orchestrate the formation and maintenance of each cell, and control the cellular phenotypes of various organismsis, is both captivating and intricate. Since the inception of the first single-cell RNA technology, technologies related to single-cell sequencing have experienced rapid advancements in recent years. These technologies have expanded horizontally to include single-cell genome, epigenome,proteome, and metabolome, while vertically, they have progressed to integrate multiple omics data and incorporate additional information such as spatial sc RNA-seq and CRISPR screening. Single-cell omics represent a groundbreaking advancement in the biomedical field,offering profound insights into the understanding of complex diseases, including cancers. Here, we comprehensively summarize recent advances in single-cell omics technologies, with a specific focus on the methodology section. This overview aims to guide researchers in selecting appropriate methods for single-cell sequencing and related data analysis.

关键词： single-cell sequencing genome epigenome proteomics metabolomics multimodal spatial transcriptomics CRISPR screening

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Advances in the treatment of autism spectrum disorder:Wharton jelly mesenchymal stem cell transplantation

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World Journal of Methodology 2025年第1期15卷 72-79页

作者： Serdar Kabatas ErdinçCivelek Eyüp Can Savrunlu Umut Karaaslan Özlem Yıldız Erdal Karaöz department of Neurosurgery University of Health Sciences TurkeyGaziosmanpaşa Training and Research HospitalIstanbul 34255Türkiye department of pediatric Allergy-Immunology Institute of Health Sciences Marmara UniversityIstanbul 34865Türkiye Center for stem cell&Gene Therapy Research and Practice University of Health Sciences TurkeyIstanbul 34255Türkiye department of Child and Adolescent Psychiatry University of Health SciencesGaziosmanpaşa Training and Research HospitalIstanbul 34255Türkiye department of Child and Adolescent Psychiatry Kocaeli University Faculty of MedicineKocaeli 41001Türkiye Center for Regenerative Medicine and stem cell Research&Manufacturing Liv HospitalIstanbul 34340Türkiye department of Histology and Embryology Istinye UniversityFaculty of MedicineIstanbul 34010Türkiye Center for stem cell and Tissue Engineering Research and Practice Istinye UniversityIstanbul 34340Türkiye

BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted *** recent studies,neuroinflammation and immune dysregulation have come to the forefront in its *** are studies suggesting that stem cell therapy may be effective in the treatment of *** To evolve the landscape of ASD treatment,focusing on the potential benefits and safety of stem cell *** A detailed case report is presented,displaying the positive outcomes observed in a child who underwent intrathecal and intravenous Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)transplantation combined with *** The study demonstrates a significant improvement in the child’s functional outcomes(Childhood Autism Rating Scale,Denver 2 Developmental Screening Test),especially in language and gross motor *** serious side effects were encountered during the 2-year *** The findings support the safety and effectiveness of WJ-MSC transplantation in managing ASD.

关键词： Autism spectrum disorder Neurorehabilitation stem cell transplantation Wharton jelly mesenchymal stem cells Inflammation

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Mid1ip1b modulates apical reorientation of non-centrosomal microtubule organizing center in epithelial cells

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Journal of Genetics and Genomics 2018年第8期45卷 433-442页

作者： Xin Zhou Chun Xiao Yu Li Yanna Shang Dongqin Yin Siying Li Bo Xiang Ran Lu Yi Ji Yang Wu Wentong Meng Hongyan Zhu Jin Liu Huozhen Hu Xianming Mo Hong Xu department of pediatric surgery and laboratory of stem cell biology State Key Laboratory of Biotherapy West China Hospital Sichuan University and Collaborative Innovation Center for Biotherapy National Clinical Research Center of Geriatrics West China Hospital Sichuan University

In most kinds of animal cells, the centrosome serves as the main microtubule organizing center （MTOC） that nucleates microtubule arrays throughout the cytoplasm to maintain cell structure, cell division and intracellular transport. Whereas in epithelial cells, non-centrosomal MTOCs are established in the apical domain for generating asymmetric microtubule fibers and cilia in epithelial cells for the organ morphogenesis during embryonic development. However, the mechanism by which MTOCs localize to the apical domain in epithelial cells remains largely unknown. Here, we show that Mid liplb has a close interaction with γ-tubulin protein, the central component of MTOC, and modulates lumen opening of the neural tube, gut, intestine, and kidney of zebrafish. Knockdown or dominant negative effect of Mid 1ip 1 b resulted in failure of lumen formation of the organs as aforementioned. Moreover, the non-centrosomal MTOCs were unable to orientate to the apical domain in Midliplb knockdown epithelial cells, and the centrosomal MTOCs were inaccurately placed in the apical domain, resulting in defective formation of asymmetric microtubules and misplacement of cilia in the apical domain. These data uncover a molecule that controls the proper localization of MTOCs in the apical domain in epithelial cells for organ morphogenesis during embryonic development.

关键词： Mid1ip1b Microtubule organizing center Non-centrosomal MTOC Microtubule Epithelial cell

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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari Jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang J.Adrian Tyndall Binu Tharakan Firas Kobeissy department of surgery Morehouse School of MedicineAtlantaGAUSA department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA department of Neurological surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA department of pediatrics Emory UniversityAtlantaGAUSA department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

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Hepatic differentiation from embryonic stem cells in vitro

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Chinese Medical Journal 2003年第12期116卷 1893-1897页

作者：胡安斌蔡继业郑启昌何晓青潘运龙李凌松 department of General surgery College Huaqiao Hospital stem cell Research Center

OBJECTIVE: To investigate an method for hepatic differentiation from embryonic stem cells (ES cells) in vitro and the resulting differentiation ratio, in order to develop a procedure for producing a new type of hepatocyte for hepatocyte replacement therapy in the treatment of liver failure. METHODS: ES cells from Balb/C mice were cultured and maintained in an undifferentiated state in gelatin-coated dishes using Dulbecco's modified Eagle's medium (DMEM) containing 1000 U/ml leukemia inhibitory factor (LIF). Then, LIF was withdrawn from the DMEM to allow the ES cells to develop into embryonic bodies (EBs). EBs were plated onto tissue culture dishes, and growth factors such as acidicfibroblast growth factor (aFGF) and hepatocyte growth factor (HGF) were added to the medium to promote directional differentiation. The course of development and differentiation was observed dynamically using an inversion microscope. The expression of hepatic proteins, such as alpha-fetoprotein (AFP), albumin (ALB), cytokeratin 8 (CK8), cytokeratin 18 (CK18), in cytoplasm was analyzed by immunocytochemistry (ICC). The concentration of ALB in the medium was determined dynamically by radioimmunoassay (RIA). RESULTS: ES cells replicated as clones, without differentiating, in DMEM containing LIF. They developed into EBs in medium without LIF. Our ICC assay showed that differentiating cells did not express hepatic proteins, such as AFP, ALB, CK8, and CK18 until day 7, day 9, day 11, and day 11, respectively (up to 2 days later when growth factors are not present). The concentration of AFP in the medium was first detected on day 8, at a concentration of 3.4 ng/ml, and increased to 22.8 ng/ml by day 15. The concentration of ALB in the medium was 0.2 micro g/ml on day 11, and increased to 2.2 micro g/ml by day 15. ALB-positive cells under ICC manifest morphological structures were consistent with normal mouse hepatocytes. The differentiation ratio of hepatocytes in the ES cell differentiation syst

关键词： Animals cell Differentiation cells, Cultured Embryo Hepatocytes Liver Mice Mice, Inbred BALB C Research Support, Non-U.S. Gov't stem cells

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Aberrant LETM1 elevation dysregulates mitochondrial functions and energy metabolism and promotes lung metastasis in osteosarcoma

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Genes & Diseases 2024年第3期11卷 368-384页

作者： Yulu Shi Quan Kang Hong Zhou Xiaohan Yue Yang Bi Qing Luo stem cell biology and Therapy laboratory The Children's Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of PediatricsChongqing 400014China department of pediatric surgery The Children's Hospital of Chongqing Medical UniversityChongqing 400014China

Osteosarcoma is a differentiation-deficient disease,and despite the unique advan-tages and great potential of differentiation therapy,there are only a few known differentia-tion inducers,and little research has been done on their *** differentiation is associated with an increase in mitochondrial content and *** metabolism of some tu-mor cells is characterized by impaired oxidative phosphorylation,as well as up-regulation of aerobic glycolysis and pentose phosphate ***-containing zipper and EF-hand transmembrane protein 1(LETM1)is involved in the maintenance of mitochondrial morphology and is closely associated with tumorigenesis and progression,as well as cancer cell *** found that MG63 and 143B osteosarcoma cells overexpress LETM1 and exhibit abnormalities in mitochondrial structure and *** of LETM1 partially restored the mitochon-drial structure and function,inhibited the pentose phosphate pathway,promoted oxidative phosphorylation,and led to osteogenic *** also inhibited spheroid cell forma-tion,proliferation,migration,and invasion in an in vitro *** LETM1 was knocked down in vivo,there was reduced tumor formation and lung *** data suggest that mitochondria are aberrant in LETM1-overexpressing osteosarcoma cells,and knockdown of LETM1 partially restores the mitochondrial structure and function,inhibits the pentose phosphate pathway,promotes oxidative phosphorylation,and increases osteogenic differentiation,thereby reducing malignant biological behavior of the cells.

关键词： Cancer metabolism Differentiation LETM1 Osteosarcoma stemness

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Adult-derived human liver stem/progenitor cells as sensors of inflammation: a potential therapy for liver disorders

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Hepatobiliary surgery and Nutrition 2019年第3期8卷 286-288页

作者： Soura Mardpour Amir Ali Hamidieh Tissue Engineering and Applied cell Sciences department School of Advanced Technologies in MedicineTehran University of Medical SciencesTehranIran department of stem cells and Developmental biology Cell Science Research CenterRoyan Institute for Stem Cell Biology and TechnologyACECRTehranIran pediatric stem cell Transplant department Children’s Medical CenterTehran University of Medical SciencesTehranIran

Advanced liver diseases remain one of the major health issues *** fibrosis,inflammatory damage,deprivation of metabolic capacity and parenchymal cell death are the main characteristics of end-stage liver *** liver transplantation has been considered as the therapy of choice in patients suffering from liver failure such as fulminant liver failure,cirrhosis and hepatocellular carcinoma(HCC).

关键词： liver damage death

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Therapeutic effect of oridonin on mice with prostate cancer

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Asian Pacific Journal of Tropical Medicine 2016年第2期9卷 182-185页

作者： Ming Ming Feng-Yin Sun Wen-Tong Zhang Ji-Ke Liu department of pediatric surgery Qilu Hospital of Shandong University department of pediatric surgery Taian City Central Hospital department of pediatric surgery Liaocheng Hospital

Objective: To investigate the therapeutic effect and the related mechanism of oridonin on mice with prostate cancer. Methods: Sixty BALB/C male nude mice were selected. A model of RM-1 cell transplantation tumor of prostate cancer was built by the subcutaneous inoculation of RM-1 cells. After that, those 60 experimental mice were randomly divided into groups A, B and C. Each group had 20 mice. Mice in group A were treated with 0.2 m L of normal saline(0.9%) by intraperitoneal injection once a day; mice in group B received intraperitoneal injection of 1.875 mg/m L of oridonin once a day; and mice in group C received intraperitoneal injection of 7.5 mg/m L of oridonin once a day. Mice in the three groups were treated uninterruptedly for 5 weeks and were all killed. Then, tumors were excised and weighed to calculate their growth inhibitory rate, volume increment and anti-tumor rate. Thymus and spleen of mice in the three groups were collected to calculate the thymus and spleen index. Immunohistochemical staining was applied to observe the expression of caspase-3 in prostate cancer tissue of mice of the three groups. Results: The qualities and volume increment of tumors in groups B and C were significantly lower than those of group A(P 0.05). Immumohistochemical staining revealed that the caspase-3 protein in prostate cancer tissue of mice of group A expressed negatively with colourless or light-colored karyon; while the caspase-3 protein in prostate cancer tissue of mice of group B expressed positively with dark-colored karyon, ce

关键词： Oridonin Prostate cancer RM-1 cells Caspase-3

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Incorporation of a Toll-like receptor 2/6 agonist potentiates mRNA vaccines against cancer and infectious diseases

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Signal Transduction and Targeted Therapy 2023年第8期8卷 3806-3817页

作者： Yangzhuo Gu Jingyun Yang Cai He Tingmei Zhao Ran Lu Jian Liu Xianming Mo Fuqiang Wen Huashan Shi department of Biotherapy State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan Universityand Collaborative Innovation Center for BiotherapyChengduSichuan 610041China Division of Pulmonary Diseases State Key Laboratory of Biotherapy and Department of Respiratory and Critical Care MedicineWest China HospitalSichuan UniversityChengduSichuan 610041China laboratory of stem cell biology and department of pediatric surgery State Key Laboratory of BiotherapyWest China HospitalSichuan Universityand Collaborative Innovation Center for BiotherapyChengduSichuan 610041China

mRNA vaccines have emerged rapidly in recent years as a prophylactic and therapeutic agent against various diseases including cancer and infectious *** of mRNA vaccines have been underway,among which boosting of efficacy is of great ***2Cys,a simple synthetic metabolizable lipoamino acid that signals through Toll-like receptor(TLR)2/6 pathway,eliciting both humoral and cellular adaptive immune responses,is an interesting candidate *** investigate the enhancement of the efficacies of mRNA vaccines by Pam2Cys,the adjuvant was incorporated into mRNA-lipid nanoparticles(LNPs)to achieve co-delivery with *** with the resulting mRNA-LNPs(Pam2Cys)shaped up the immune milieu in the draining lymph nodes(dLNs)through the induction of IL-12 and IL-17,among other *** presentation was carried out mainly by migratory and dLNresident conventional type 2 DCs(cDC2s)and significantly more potent antitumor responses were triggered in both prophylactic and therapeutic tumor models in a CD4^(+) and CD8^(+) T cell-dependent *** memory antitumor immunity was also ***,the vaccine also stimulated much more robust humoral and cellular immunity in a surrogate COVID-19 prophylactic *** but not the least,the new vaccines exhibited good preliminary safety profiles in murine *** facts warrant future development of Pam2Cys-incorporated mRNA vaccines or relevant mRNA therapeutics for clinical application.

关键词： vaccines immunity diseases

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