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Domesticated cynomolgus monkey embryonic stem cells allow the generation of neonatal interspecies chimeric pigs

Protein & Cell 2020年第2期11卷 97-107页

作者： Rui Fu Dawei Yu Jilong Ren Chongyang Li Jing Wang Guihai Feng Xuepeng Wang Haifeng Wan Tianda Li Libin Wang Ying Zhang Tang Hai Wei Li Qi Zhou State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China institute for Stem Cell and regeneration Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Blastocyst complementation by pluripotent stem cell(PSC)injection is believed to be the most promising method to generate xenogeneic ***,ethical issues prevent the study of human chimeras in the late embryonic stage of *** embryonic stem cells(ESCs),which have similar pluripotency to human ESCs,are a good model for studying interspecies chimerism and organ ***,whether primate ESCs can be used in xenogenous grafts remains *** this study,we evaluated the chimeric ability of cynomolgus monkey(Macaca fascicularis)ESCs(cmESCs)in pigs,which are excellent hosts because of their many similarities to *** report an optimized culture medium that enhanced the anti-apoptotic ability of cmESCs and improved the development of chimeric embryos,in which domesticated cmESCs(D-ESCs)injected into pig blastocysts differentiated into cells of all three germ *** addition,we obtained two neonatal interspecies chimeras,in which we observed tissue-specific D-ESC *** together,the results demonstrate the capability of D-ESCs to integrate and differentiate into functional cells in a porcine model,with a chimeric ratio of 0.001-0.0001 in different neonate *** believe this work will facilitate future developments in xenogeneic organogenesis,bringing us one step closer to producing tissue-specific functional cells and organs in a large animal model through interspecies blastocyst complementation.

关键词： embryonic stem cells,blastocyst complementation cynomolgus monkey pig interspecies chimera organ reconstruction

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Current advances in haploid stem cells

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Protein & Cell 2020年第1期11卷 23-33页

作者： Tongtong Cui Zhikun Li Qi Zhou Wei Li State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China institute for Stem Cell and regeneration Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Diploidy is the typical genomic mode in all *** stem cells are artificial cell lines experimentally derived in vitro in the form of different types of stem cells,which combine the characteristics of haploidy with a broad developmental potential and open the possibility to uncover biological mysteries at a genomic *** date,a multitude of haploid stem cell types from mouse,rat,monkey and humans have been derived,as more are in *** have been applied in high-throughput genetic screens and mammalian assisted ***,we review the generation,unique properties and broad applications of these remarkable cells.

关键词： haploidy parthenogenetic androgenetic stem cells diploidization functional genomics imprinting

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Mechanisms underlying the promotion of functional recovery by deferoxamine after spinal cord injury in rats

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Neural regeneration Research 2017年第6期12卷 959-968页

作者： Jian Hao Bo Li Hui-quan Duan Chen-xi Zhao Yan Zhang Chao Sun Bin Pan Chang Liu Xiao-hong Kong Xue Yao Shi-qing Feng Department of Orthopedics Tianjin Medical University General Hospital School of Medicine Nankai University Tianjin Neurological institute Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System Ministry of Education

Deferoxamine, a clinically safe drug used for treating iron overload, also repairs spinal cord injury although the mechanism for this action remains unknown. Here, we determined whether deferoxamine was therapeutic in a rat model of spinal cord injury and explored potential mechanisms for this effect. Spinal cord injury was induced by impacting the spinal cord at the thoracic T10 vertebra level. One group of injured rats received deferoxamine, a second injured group received saline, and a third group was sham operated. Both 2 days and 2 weeks after spinal cord injury, total iron ion levels and protein expression levels of the proinflammatory cytokines tumor necrosis factor-α and interleukin-1β and the pro-apoptotic protein caspase-3 in the spinal cords of the injured deferoxamine-treated rats were significantly lower than those in the injured saline-treated group. The percentage of the area positive for glial fibrillary acidic protein immunoreactivity and the number of terminal deoxynucleotidyl transferase d UTP nick end labeling-positive cells were also significantly decreased both 2 days and 2 weeks post injury, while the number of Neu N-positive cells and the percentage of the area positive for the oligodendrocyte marker CNPase were increased in the injured deferoxamine-treated rats. At 14–56 days post injury, hind limb motor function in the deferoxamine-treated rats was superior to that in the saline-treated rats. These results suggest that deferoxamine decreases total iron ion, tumor necrosis factor-α, interleukin-1β, and caspase-3 expression levels after spinal cord injury and inhibits apoptosis and glial scar formation to promote motor function recovery.

关键词： injured interleukin glial caspase saline underlying fibrillary minutes acidic neuronal

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Insulin-like growth factor 1 partially rescues early developmental defects caused by SHANK2 knockdown in human neurons

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Neural regeneration Research 2020年第12期15卷 2335-2343页

作者： Shu-Ting Chen Wan-Jing Lai Wei-Jia Zhang Qing-Pei Chen Li-Bing Zhou Kwok-Fai So Ling-Ling Shi Guangdong-Hong Kong-Macao institute of CNS regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhouGuangdong ProvinceChina Clinical Medicine Jinan UniversityGuangzhouGuangdong ProvinceChina Department of Psychiatry the First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina

SHANK2 is a scaffold protein that serves as a protein anchor at the postsynaptic density in *** variants of SHANK2 are strongly associated with synaptic dysfunction and the pathophysiology of autism spectrum *** studies indicate that early neuronal developmental defects play a role in the pathogenesis of autism spectrum disorder,and that insulin-like growth factor 1 has a positive effect on neurite *** investigate the effects of SHANK2 knockdown on early neuronal development,we generated a sparse culture system using human induced pluripotent stem cells,which then differentiated into neural progenitor cells after 3–14 days in culture,and which were dissociated into single *** in the experimental group were infected with shSHANK2 lentivirus carrying a red fluorescent protein reporter(shSHANK2 group).Control neurons were infected with scrambled sh Control lentivirus carrying a red fluorescent protein reporter(sh Control group).Neuronal somata and neurites were reconstructed based on the lentiviral red fluorescent protein *** dendritic and motility changes in VGLUT1^+glutamatergic neurons and TH+dopaminergic neurons were then evaluated in both *** with sh Control VGLUT1^+neurons,the dendritic length and arborizations of shSHANK2 VGLUT1^+neurons were shorter and fewer,while cell soma speed was ***,dendritic length and arborization were significantly increased after insulin-like growth factor 1 treatment of shSHANK2 neurons,while cell soma speed remained *** results suggest that insulin-like growth factor 1 can rescue morphological defects,but not the change in neuronal ***,our findings demonstrate that SHANK2 deficiency perturbs early neuronal development,and that IGF1 can partially rescue the neuronal defects caused by SHANK2 *** experimental procedures and protocols were approved by the Laboratory Animal Ethics Committee of Jinan Universi

关键词： cells factor growth in vitro model neural differentiation neurogenesis plasticity

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Brain scarring in infants:immunological insights from a neonatal hypoxic-ischemic encephalopathy model

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Neural regeneration Research 2025年第10期20卷 2909-2910页

作者： Pedro Moreno Pimentel-Coelho Carlos Chagas Filho Biophysics institute Federal University of Rio de JaneiroRio de JaneiroBrazil

Neonatal hypoxic-ischemic encephalopathy(HIE)is a significant cause of disability in *** brain function and accelerating neurological recovery may require a combination of neuroprotective and pro-regenerative treatments at different stages of *** the first hours after the neonatal insult are the most critical period for neuroprotection,the existence of secondary and tertiary mechanisms of brain injury offers the possibility of preventing delayed neurodegeneration in the subsequent days,weeks,or months(Levison et al.,2022).

关键词： neonatal protective hypoxic

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New glucocerebrosidase antibodies can advance research in the field of neurodegenerative disorders

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Neural regeneration Research 2025年第4期20卷 1085-1086页

作者： Charis Ma Krystyna Rytel Yu Chen Ellen Sidransky Medical Genetics Branch National Human Genome Research InstituteNational Institutes of HealthBethesdaMDUSA

In medical research,there are times when the introduction of a new tool can launch scientific discovery in new *** antibody development may be considered mundane,in the field of glucocerebrosidase(GCase)research,the dearth of validated antibodies for different applications has impeded progress in studies of disease pathogenesis and therapeutic *** recent introduction of new,rigorously evaluated antibodies can now propel research into the link between glucocerebrosidase and Parkinson’s disease(PD)as well as aspects of the pathobiology of Gaucher disease(Jong et al.,2024).

关键词： antibodies cerebro

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International collaboration for global accessibility of COVID-19 vaccines

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National Science Review 2020年第8期7卷 1269-1269页

作者： Qi Zhou institute for Stem Cell and regeneration Chinese Academy of Sciences NSR

The novel coronavirus has been spreading and has currently affected over 200 countries and territories across the ***, up to now, there is still no cure for COVID-19. Not surprisingly, the vaccine is considered the ultimate solution to the coronavirus pandemic and it is believed that there has never been a more urgent task than creating broad immunity against the coronavirus.

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Comparison of the Histological Morphology between Normal Skin and Scar Tissue

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2016年第2期36卷 265-269页

作者：杨少伟耿志军马奎孙晓艳付小兵 Wound Healing and Cell Biology Laboratory Institute of Basic Medical ScienceTrauma Center of Postgraduate Medical SchoolChinese PLA General Hospital Key Research Laboratory of Tissue Repair and regeneration of PLA and Beijing Key Research Laboratory of Skin InjuryRepair and RegenerationFirst Affiliated Hospital to the Chinese PLA General Hospital

Skin wound healing is a complex event, and interrupted wound healing process could lead to scar formation. The aim of this study was to examine the morphological changes of scar tissue. Pathological staining（HE staining, Masson＇s trichrome staining, methenamine silver staining） was used to evaluate the morphological changes of regenerating epidermis in normal skin and scar tissue, and immunofluorescence staining to detect the expression of collagen Ⅳ, a component of basement membrane（BM）, and the expression of integrinβ4, a receptor for BM laminins. Additionally, the expression of CK14, CK5, and CK10 was measured to evaluate the proliferation and differentiation of keratinocytes in normal skin and scar tissue. The results showed that the structure of the skin was histologically changed in scar tissue. Collagen Ⅳ, expressed under the epidermis of normal skin, was reduced distinctly in scar tissue. Integrinβ4, expressed in the basal layer of normal skin, was found absent in the basal layer of scar tissue. Additionally, it was found that keratinocytes in scarring epidermis were more proliferative than in normal skin. These results indicate that during the skin wound healing, altered formation of BM may affect the proliferation of keratinocytes, reepithelial and tissue remodeling, and then result in scar formation. Thus, remodeling BM structure during wound repair may be beneficial for improving healing in cutaneous wounds during clinical practice.

关键词： histological morphology basement membrane keratinocyte epidermis wound healing

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Decreased numbers of circulating endothelial progenitor cells are associated with hyperglycemia in patients with traumatic brain injury

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Neural regeneration Research 2019年第6期14卷 984-990页

作者： Hui-Jie Wei Li Liu Fang-Lian Chen Dong Wang Liang Wang Zeng-Guang Wang Rong-Cai Jiang Jing-Fei Dong Jie-Li Chen Jian-Ning Zhang Department of Neurosurgery Tianjin Medical University General HospitalTianjin Neurological InstituteKey Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous SystemMinistry of EducationTianjin Key Laboratory of InjuriesVariations and Regeneration of Nervous System Department of Neurosurgery Peking University International Hospital Thrombosis Research Section Department of MedicineBaylor College of Medicine Department of Neurology Henry Ford Health System

Hyperglycemia reduces the number of circulating endothelial progenitor cells, accelerates their senescence and impairs their ***, the relationship between blood glucose levels and endothelial progenitor cells in peripheral blood of patients with traumatic brain injury is unclear. In this study, 101 traumatic brain injury patients admitted to the Department of Neurosurgery, Tianjin Medical University General Hospital or the Department of Neurosurgery, Tianjin Huanhu Hospital, China, were enrolled from April 2005 to March 2007. The number of circulating endothelial progenitor cells and blood glucose levels were measured at 1, 4, 7, 14 and 21 days after traumatic brain injury by flow cytometry and automatic biochemical analysis, respectively. The number of circulating endothelial progenitor cells and blood sugar levels in 37 healthy control subjects were also examined. Compared with controls, the number of circulating endothelial progenitor cells in traumatic brain injury patients was decreased at 1 day after injury, and then increased at 4 days after injury,and reached a peak at 7 days after injury. Compared with controls, blood glucose levels in traumatic brain injury patients peaked at 1 day and then decreased until 7 days and then remained stable. At 1, 4, and 7 days after injury, the number of circulating endothelial progenitor cells was negatively correlated with blood sugar levels(r =-0.147, P < 0.05). Our results verify that hyperglycemia in patients with traumatic brain injury is associated with decreased numbers of circulating endothelial progenitor cells. This study was approved by the Ethical Committee of Tianjin Medical University General Hospital, China(approval No. 200501) in January 2015.

关键词： nerve regeneration endothelial progenitor cells vascular repair vascular remodeling angiogenesis neovascularization blood glucose hyperglycemia traumatic brain injury mobilization suppression senescence alternative therapy brain damage neural regeneration

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Dynamic changes in growth factor levels over a 7-day period predict the functional outcomes of traumatic brain injury

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Neural regeneration Research 2018年第12期13卷 2134-2140页

作者： Shuai Zhou Dong-Pei Yin Yi Wang Ye Tian Zeng-Guang Wang Jian-Ning Zhang Department of Intensive Care Unit Tianjin Medical University General Hospital Tianjin China Tianjin Neurological institute Tianjin China Key Laboratory of Post-Trauma Neuro-Repair and regeneration in Central Nervous System Ministry of Education Tianjin China Tianjin Key Laboratory of Injuries Variations and Regeneration of Nervous System Tianjin China Department of Neurosurgery Tianjin Medical University General Hospital Tianjin China

Traumatic brain injury（TBI） can result in poor functional outcomes and death, and overall outcomes are varied. Growth factors, such as angiopoietin-1（Ang-1）, vascular endothelial growth factor（VEGF）, and granulocyte-colony stimulating factor（G-CSF）, play important roles in the neurological functions. This study investigated the relationship between serum growth factor levels and long-term outcomes after TBI. Blood samples from 55 patients were collected at 1, 3 and 7 days after TBI. Blood samples from 39 healthy controls were collected as a control group. Serum Ang-1, G-CSF, and VEGF levels were measured using ELISA. Patients were monitored for 3 months using the Glasgow Outcome Scale-Extended（GOSE）. Patients having a GOSE score of 〉 5 at 3 months were categorized as a good outcome, and patients with a GOSE score of 1-5 were categorized as a bad outcome. Our data demonstrated that TBI patients showed significantly increased growth factor levels within 7 days compared with healthy controls. Serum levels of Ang-1 at 1 and 7 days and G-CSF levels at 7 days were significantly higher in patients with good outcomes than in patients with poor outcomes. VEGF levels at 7 days were remarkably higher in patients with poor outcomes than in patients with good outcomes. Receiver operating characteristic analysis showed that the best cut-off points of serum growth factor levels at 7 days to predict functional outcome were 1,333 pg/mL for VEGF, 447.2 pg/mL for G-CSF, and 90.6 ng/mL for Ang-1. These data suggest that patients with elevated levels of serum Ang-1, G-CSF, and decreased VEGF levels had a better prognosis in the acute phase of TBI（within 7 days）. This study was registered with the Chinese Clinical Trial Registry（registration number： ChiCTR1800018251） on September 7, 2018.

关键词： nerve regeneration traumatic brain injury vascular endothelial growth factor angiopoietin-1 granulocyte-colony stimulating factor outcomes secondary brain injuries blood-brain barrier brain edema acute phase clinical trial neural regeneration

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