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A novel mouse model of central cord syndrome

Neural Regeneration research 2023年第12期18卷 2751-2756页

作者： Elzat Elham-Yilizati Yilihamu Xiangchuang Fan Zimeng Yang Shiqing Feng Department of Orthopedics Qilu Hospital of Shandong UniversityJinanShandong ProvinceChina Department of Orthopedics Tianjin Medical University General HospitalTianjinChina

Patients with potential spinal stenosis are susceptible to central cord syndrome induced by blunt trauma.Suitable animal models are helpful for studying the pathogenesis and treatment of such injuries.In this study,we established a mouse model of acute blunt traumatic spinal cord injury by compressing the C6 spinal cord with 5 and 10 g/mm~2 compression weights to simulate cervical central cord syndrome.Behavioral testing confirmed that this model exhibited the characteristics of central cord syndrome because motor function in the front paws was impaired,whereas basic motor and sensory functions of the lower extremities were retained.Hematoxylin-eosin staining showed that the diseased region of the spinal cord in this mouse model was restricted to the gray matter of the central cord,whereas the white matter was rarely affected.Magnetic resonance imaging showed a hypointense signal in the lesion after mild and severe injury.In addition,immunofluorescence staining showed that the degree of nerve tract injury in the spinal cord white matter was mild,and that there was a chronic inflammation reaction.These findings suggest that this mouse model of central cord syndrome can be used as a model for preclinical research,and that gray matter is most vulnerable to injury in central cord syndrome,leading to impaired motor function.

关键词： animal model behavior central cord syndrome cervical spinal cord injury cervical spinal cord pathology preclinical research spinal cord spinal cord compression spinal cord injury

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Progress,implications,and challenges in using humanized immune system mice in CAR-T therapy-Application evaluation and improvement

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Animal Models and Experimental Medicine 2024年第1期7卷 3-11页

作者： Hanwei Yue Lin Bai NHC Key Laboratory of Human Disease Comparative Medicine Institute of Laboratory Animal SciencesCAMS and PUMCChao-yang DistrictBeijingChina

In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking the human immune system and the tumor immune microenvironment,compared to traditional immunodeficient mice.To better promote the application of HIS mice in preclinical research,we se-lectively summarize the current prevalent and breakthrough research and evaluation of chimeric antigen receptor(CAR)-T cells in various antiviral and antitumor treat-ments.By exploring its application in preclinical research,we find that it can better reflect the actual clinical patient condition,with the advantages of providing high-efficiency detection indicators,even for progressive research and development.We believe that it has better clinical patient simulation and promotion for the updated design of CAR-T cell therapy than directly transplanted immunodeficient mice.The characteristics of the main models are proposed to improve the use defects of the existing models by reducing the limitation of antihost reaction,combining multiple models,and unifying sources and organoid substitution.Strategy study of relapse and toxicity after CAR-T treatment also provides more possibilities for application and development.

关键词： antitumor antiviral CAR-T humanized immune system model humanized mice preclinical research

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A novel long-term intravenous combined with local treatment with human amnion-derived mesenchymal stem cells for a multidisciplinary rescued uremic calciphylaxis patient and the underlying mechanism

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Journal of Molecular Cell Biology 2022年第2期14卷 56-71页

作者： Lianju Qin Jing Zhang Yujie Xiao Kang Liu Yugui Cui Fangyan Xu Wenkai Ren Yanggang Yuan Chunyan Jiang Song Ning Xiaoxue Ye Ming Zeng Hanyang Qian Anning Bian Fan Li Guang Yang Shaowen Tang Zhihong Zhang Juncheng Dai Jing Guo Qiang Wang Bin Sun Yifei Ge Chun Ouyang Xueqiang Xu Jing Wang Yaoyu Huang Hongqing Cui Jing Zhou Meilian Wang Zhonglan Su Yan Lu Di Wu Jingping Shi Wei Liu Li Dong Yinbing Pan Baiqiao Zhao Ying Cui Xueyan Gao Zhanhui Gao Xiang Ma Aiqin Chen Jie Wang Meng Cao Qian Cui Li Chen Feng Chen Youjia Yu Qiang Ji Zhiwei Zhang Mufeng Gu Xiaojun Zhuang Xiaolin Lv Hui Wang Yanyan Pan Ling Wang Xianrong Xu Jing Zhao Xiuqin Wang Cuiping Liu Ningxia Liang Changying Xing Jiayin Liu Ningning Wang State Key Laboratory of Reproductive Medicine Center of Clinical Reproductive MedicineThe First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing 210029China Department of Nephrology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing 210029China Department of Epidemiology and Biostatistics School of Public HealthNanjing Medical UniversityNanjing 211166China Department of Pathology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing 210029China Department of Cardiology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing 210029China Department of Rheumatology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing 210029China Department of Obstetrics The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing 210029China Department of Dermatology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing 210029China Department of Burn and Plastic Surgery The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing 210029China Department of Nuclear Medicine The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing 210029China Department of Infection The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing 210029China Department of Anesthesiology and Pain Management The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing 210029China Department of Nephrology The First People’s Hospital of LianyungangLianyungang 222061China Department of Nephrology Northern Jiangsu People’s HospitalYangzhou 225001China Department of General Medicine Geriatric Hospital of Nanjing Medical UniversityNanjing 210024China Department of Nephrology BenQ Medical CenterThe Affiliated BenQ Hospital of Nanjing Medical Uni

Calciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis,with high mortality and no proven therapy.Here,we reported a severe uremic calciphylaxis patient with progressive skin ischemia,large areas of painful malodorous ulcers,and mummified legs.Because of the worsening symptoms and signs refractory to conventional therapies,treatment with human amnion-derived mesenchymal stem cells(hAMSCs)was approved.preclinical release inspections of hAMSCs,efficacy,and safety assessment,including cytokine secretory ability,immunocompetence,tumorigenicity,and genetics analysis in vitro,were introduced.We further performed acute and long-term hAMSC toxicity evaluations in C57BL/6 mice and rats,abnormal immune response tests in C57BL/6 mice,and tumorigenicity tests in neonatal Balbc-nu nude mice.After the preclinical research,the patient was treated with hAMSCs by intravenous and local intramuscular injection and external supernatant application to the ulcers.When followed up to 15 months,the blood-based markers of bone and mineral metabolism improved,with skin soft tissue regeneration and a more favorable profile of peripheral blood mononuclear cells.Skin biopsy after 1-month treatment showed vascular regeneration with mature noncalcified vessels within the dermis,and 20 months later,the re-epithelialization restored the integrity of the damaged site.No infusion or local treatment-related adverse events occurred.Thus,this novel long-term intravenous combined with local treatment with hAMSCs warrants further investigation as a potential regenerative treatment for uremic calciphylaxis due to effects of inhibiting vascular calcification,stimulating angiogenesis and myogenesis,anti-inflammatory and immune modulation,multidifferentiation,re-epithelialization,and restoration of integrity.

关键词： calciphylaxis chronic kidney disease vascular calcification multidisciplinary rescue human amnion-derived mesenchymal stem cells preclinical research regenerative medicine

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