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Establishment of a Fah-LSL mouse model to study BEC-to-hepatocyte conversion

Biophysics Reports 2023年第6期9卷 309-324页

作者： Xingrui Wang Wenjuan Pu Huan Zhu Mingjun Zhang Bin Zhou New Cornerstone Science Laboratory State Key Laboratory of Cell Biology Shanghai Institute of Biochemistry and Cell Biology Center for Excellence in Molecular Cell Science Chinese Academy of Sciences University of Chinese Academy of Sciences Key Laboratory of Systems Health Science of Zhejiang Province School of Life Science Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences School of Life Science and Technology Shanghai Tech University

The liver consists predominantly of hepatocytes and biliary epithelial cells(BECs), which serve distinct physiological functions. Although hepatocytes primarily replenish their own population during homeostasis and injury repair, recent findings have suggested that BECs can transdifferentiate into hepatocytes when hepatocyte-mediated liver regeneration is impaired. However, the cellular and molecular mechanisms governing this BEC-to-hepatocyte conversion remain poorly understood largely because of the inefficiency of existing methods for inducing lineage conversion. Therefore, this study introduces a novel mouse model engineered by the Zhou’s lab, where hepatocyte senescence is induced by the deletion of the fumarylacetoacetate(Fah) gene. This model facilitates the efficient conversion of BECs to hepatocytes and allows for the simultaneous lineage tracing of BECs; consequently, a transitional liver progenitor cell population can be identified during lineage conversion. This study also outlines the technical procedures for utilizing this model to determine the underlying cellular and molecular mechanisms of BEC-to-hepatocyte conversion and provides new insights into liver regeneration and its underlying molecular mechanism.

关键词： Liver regeneration BEC-to-hepatocyte transdifferentiation Fumarylacetoacetate (Fah) gene Transitional liver progenitor cells (TLPC) Lineage tracing

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Continuous purification and culture of rat type 1 and type 2 alveolar epithelial cells by magnetic cell sorting

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Chinese Journal of Traumatology 2022年第3期25卷 138-144页

作者： Di Liu Jian-Hui Sun Hua-Cai Zhang Jian-Xin Jiang Ling Zeng State Key Laboratory of Trauma Bums and Combined InjuriesDoping HospitalArmy Medical UniversityChongqing400042China Medical center of Trauma and War Injury Daping HospitalArmy Medical UniversityChongqing400042China

Purpose:The incidence of acute lung injury(ALI)in severe trauma patients is 48%and the mortality rate following acute respiratory distress syndrome evolved from ALI is up to 68.5%.Alveolar epithelial type 1 cells(AEC1 s)and type 2 cells(AEC2s)are the key cells in the repair of injured lungs as well as fetal lung ***,the purification and culture of AECls and AEC2s play an important role in the research of repair and regeneration of lung ***:Sprague-Dawley rats(3-4 weeks,120-150 g)were purchased for *** and DNase I were jointly used to digest lung tissue to obtain a single-cell suspension of whole lung cells,and then magnetic bead cell sorting was performed to isolate Tla positive cells as AECls from the single-cell suspension by using polyclonal rabbit anti-Tla(a specific AECls membrane protein)antibodies combined with anti-rabbit IgG ***,alveolar epithelial cell membrane marker protein EpCAM was designed as a key label to sort AEC2s from the remaining Tla-neg cells by another positive immunomagnetic selection using monoclonal mouse anti-EpCAM antibodies and anti-mouse IgG *** purity was identified by immunofluorescence staining and flow ***沾••The purity of AECls and AEC2s was 88.3%±3.8%and 92.6%±2.7%,*** cell growth was observed as follows:AECls stretched within the 12-16 h,but the cells proliferated slowly;while AEC2s began to stretch after 24 h and proliferated rapidly from the 2nd day and began to differentiate after 3 ***:AECls and AEC2s sorted by this method have high purity and good ***,our method provides a new approach for the isolation and culture of AECls and AEC2s as well as a new strategy for the research of lung repair and regeneration.

关键词： Alveolar epithelial cells type 1 Alveolar epithelial cells type 2 Three-dimensional culture Magnetic activated cell sorting

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Hierarchical macro-microporous WPU-ECM scaffolds combined with Microfracture Promote in Situ Articular Cartilage regeneration in Rabbits

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Bioactive Materials 2021年第7期6卷 1932-1944页

作者： Mingxue Chen YangYang Li Shuyun Liu Zhaoxuan Feng Hao Wang Dejin Yang Weimin Guo Zhiguo Yuan Shuang Gao Yu Zhang Kangkang Zha Bo Huang Fu Wei Xinyu Sang Qinyu Tian Xuan Yang Xiang sui Yixin Zhou Yufeng Zheng Quanyi Guo Department of Orthopaedic Surgery Peking University Fourth School of Clinical MedicineBeijing Jishuitan HospitalNo.31 Xinjiekou East StreetXicheng DistrictBeijing100035People’s Republic of China Institute of Orthopedics Chinese PLA General HospitalBeijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma&War Injuries PLANo.28 Fuxing RoadHaidian DistrictBeijing100853People’s Republic of China Academy for Advanced Interdisciplinary Studies Peking UniversityNo.5 Yiheyuan RoadHaidian DistrictBeijing100871People’s Republic of China School of Material Science and Engineering University of Science and Technology BeijingNo.30 Xueyuan RoadHaidian DistrictBeijing100083People’s Republic of China Department of Bone and Joint Surgery The Affiliated Hospital of Southwest Medical UniversityNo.25 Taiping RoadLuzhou646000People’s Republic of China Department of Materials Science and Engineering College of EngineeringPeking UniversityNo.5 Yiheyuan RoadHaidian DistrictBeijing100871China

tissue engineering provides a promising avenue for treating cartilage ***,great challenges remain in the development of structurally and functionally optimized scaffolds for cartilage repair and *** this study,decellularized cartilage extracellular matrix(ECM)and waterborne polyurethane(WPU)were employed to construct WPU and WPU-ECM scaffolds by water-based 3D printing using low-temperature deposition manufacturing(LDM)system,which combines rapid deposition manufacturing with phase separation *** scaffolds successfully achieved hierarchical macro-microporous *** adding ECM,WPU scaffolds were markedly optimized in terms of porosity,hydrophilia and bioactive ***,the optimized WPU-ECM scaffolds were found to be more suitable for cell distribution,adhesion,and proliferation than the WPU *** importantly,the WPU-ECM scaffold could facilitate the production of glycosaminoglycan(GAG)and collagen and the upregulation of cartilage-specific *** results indicated that the WPU-ECM scaffold with hierarchical macro-microporous structures could recreate a favorable microenvironment for cell adhesion,proliferation,differentiation,and ECM *** vivo studies further revealed that the hierarchical macro-microporous WPU-ECM scaffold combined with the microfracture procedure successfully regenerated hyaline cartilage in a rabbit *** months after implantation,the repaired cartilage showed a similar histological structure and mechanical performance to that of normal *** conclusion,the hierarchical macro-microporous WPU-ECM scaffold may be a promising candidate for cartilage tissue engineering applications in the future.

关键词： Extracellular matrix Waterborne polyurethane Low-temperature deposition manufacturing Articular cartilage tissue engineering

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Withaferin A inhibits ferroptosis and protects against intracerebral hemorrhage

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Neural regeneration Research 2023年第6期18卷 1308-1315页

作者： Zi-Xian Zhou Qi Cui Ying-Mei Zhang Jia-Xin Yang Wen-Jing Xiang Ning Tian Yan-Lin Jiang Mei-Ling Chen Bin Yang Qing-Hua Li Ru-Jia Liao Laboratory of Neuroscience Affiliated Hospital of Guilin Medical UniversityGuilin Medical UniversityGuilinGuangxi Zhuang Autonomous RegionChina Department of Neurology Affiliated Hospital of Guilin Medical UniversityGuilin Medical UniversityGuilinGuangxi Zhuang Autonomous RegionChina Guangxi Clinical Research center for Neurological Diseases Affiliated Hospital of Guilin Medical UniversityGuilin Medical UniversityGuilinGuangxi Zhuang Autonomous RegionChina Department of Pharmacology Affiliated Hospital of Guilin Medical UniversityGuilin Medical UniversityGuilinGuangxi Zhuang Autonomous RegionChina

Recent studies have indicated that suppressing oxidative stress and ferroptosis can considerably improve the prognosis of intracerebral hemorrhage(ICH).Withaferin A(WFA),a natural compound,exhibits a positive effect on a number of neurological ***,the effects of WFA on oxidative stress and ferroptosis-mediated signaling pathways to ICH remain *** this study,we investigated the neuroprotective effects and underlying mechanism for WFA in the regulation of ICH-induced oxidative stress and *** established a mouse model of ICH by injection of autologous tail artery blood into the caudate nucleus and an in vitro cell model of hemin-induced *** was injected intracerebroventricularly at 0.1,1 or 5μg/kg once daily for 7 days,starting immediately after ICH *** markedly reduced brain tissue injury and iron deposition and improved neurological function in a dose-dependent manner 7 days after cerebral *** in vitro experiments,cell viability test showed that WFA protected SH-SY5Y neuronal cells against hemin-induced cell ***-linked immunosorbent assays in vitro and in vivo showed that WFA markedly decreased the level of malondialdehyde,an oxidative stress marker,and increased the activities of anti-oxidative stress markers superoxide dismutase and glutathione peroxidase after *** blot assay,quantitative polymerase chain reaction and immunofluorescence results demonstrated that WFA activated the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling axis,promoted translocation of Nrf2 from the cytoplasm to nucleus,and increased HO-1 *** Nrf2 with siRNA completely reversed HO-1 expression,oxidative stress and protective effects of ***,WFA reduced hemin-induced ***,after treatment with an HO-1 inhibitor,the neuroprotective effects of WFA against hemin-induced ferroptosis were *** test results showed that WFA combined with ferrostatin-1

关键词： behavior brain injuries hemorrhagic stroke ferroptosis heme oxygenase-1 neuroprotection nuclear factor E2-related factor 2 nuclear translocator oxidative stress stroke

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3D printing of functional bioengineered constructs for neural regeneration: a review

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International Journal of Extreme Manufacturing 2023年第4期5卷 87-118页

作者： Hui Zhu Cong Yao Boyuan Wei Chenyu Xu Xinxin Huang Yan Liu Jiankang He Jianning Zhang Dichen Li State Key Laboratory for Manufacturing Systems Engineering Xi’an Jiaotong UniversityXi’an 710049People’s Republic of China NMPA Key Laboratory for Research and Evaluation of Additive Manufacturing Medical Devices Xi’an Jiaotong UniversityXi’an 710049People’s Republic of China Department of Neurosurgery The First Medical CenterChinese PLA General HospitalBeijing 100853People’s Republic of China

Three-dimensional(3D)printing technology has opened a new paradigm to controllably and reproducibly fabricate bioengineered neural constructs for potential applications in repairing injured nervous tissues or producing in vitro nervous tissue ***,the complexity of nervous tissues poses great challenges to 3D-printed bioengineered analogues,which should possess diverse architectural/chemical/electrical functionalities to resemble the native growth microenvironments for functional neural *** this work,we provide a state-of-the-art review of the latest development of 3D printing for bioengineered neural *** 3D printing techniques for neural tissue-engineered scaffolds or living cell-laden constructs are summarized and compared in terms of their unique *** highlight the advanced strategies by integrating topographical,biochemical and electroactive cues inside 3D-printed neural constructs to replicate in vivo-like microenvironment for functional neural *** typical applications of 3D-printed bioengineered constructs for in vivo repair of injured nervous tissues,bio-electronics interfacing with native nervous system,neural-on-chips as well as brain-like tissue models are *** challenges and future outlook associated with 3D printing for functional neural constructs in various categories are discussed.

关键词： 3D printing bioengineered neural constructs neural regeneration nerve tissue engineering nervous tissue models

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迁移的雪旺细胞指导周围神经桥内的轴突再生

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神经损伤与功能重建 2021年第9期16卷 F0003-F0003页

作者： Qing Min David B Parkinson Xin-Peng Dun 杜一星(编译) School of Pharmacy Hubei University of Science and TechnologyXianningHubei ProvincePeople's Republic of China Peninsula Medical School Faculty of HealthPlymouth UniversityPlymouthDevonUK The Co-innovation center of Neuroregeneration Nantong UniversityNantongJiangsu ProvincePeople's Republic of China 不详

周围神经系统内的雪旺细胞具有强大的再生潜力。目前的研究表明,周围神经相关的雪旺细胞具有促进多种组织修复的能力,包括周围神经间隙桥接、皮肤伤口愈合、指尖修复以及牙齿再生。专门修复的雪旺细胞的关键特征之一是它们变得高度能动... 详细信息

周围神经系统内的雪旺细胞具有强大的再生潜力。目前的研究表明,周围神经相关的雪旺细胞具有促进多种组织修复的能力,包括周围神经间隙桥接、皮肤伤口愈合、指尖修复以及牙齿再生。专门修复的雪旺细胞的关键特征之一是它们变得高度能动。它们不仅迁移到受损组织区域,成为组织再生的关键组成部分,还分泌信号分子来吸引巨噬细胞,支持神经元存活,促进轴突再生,激活局部间充质干细胞,并与其他细胞类型相互作用。目前,迁移性雪旺细胞在组织再生中的重要性在周围神经横断损伤的情况证据最为充分。神经横断后,来自近端和远端神经残端的雪旺氏细胞均迁移到神经桥中并形成雪旺细胞索以引导轴突再生。神经桥中雪旺细胞索的形成是横断损伤后周围神经成功修复的关键。本篇综述首先探讨了神经桥的形成以及神经桥中雪旺细胞迁移的行为,然后讨论迁移的雪旺细胞如何将再生轴突引导到远端神经中。我们还回顾了目前对可激活雪旺细胞迁移的信号以及雪旺细胞用于指导轴突再生的信号的理解。了解雪旺细胞迁移的分子机制可能为周围神经修复提供新的治疗策略。

关键词：轴突再生迁移神经桥雪旺细胞信号横断损伤

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Mechanobiomaterials: Harnessing mechanobiology principles for tissuerepair and regeneration

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Mechanobiology in medicine 2024年第3期2卷 64-82页

作者： Xiao Lin Hua Yang Yi Xia Kang Wu Fengcheng Chu Huan Zhou Huajian Gao Lei Yang Orthopedic Institute Department of OrthopedicsThe First Affiliated HospitalSoochow UniversitySuzhouChina School of Mechanical Engineering Hebei University of TechnologyTianjinChina center for Health Sciences and Engineering(CHSE) Hebei Key Laboratory of Biomaterials and Smart TheranosticsSchool of Health Sciences and Biomedical EngineeringHebei University of TechnologyTianjinChina Mechano-X Institute Applied Mechanics LaboratoryDepartment of Engineering MechanicsTsinghua UniversityBeijingChina

Mechanical stimuli are known to play critical roles in mediating tissue repair and regeneration. Recently, thisknowledge has led to a paradigm shift toward proactive programming of biological functionalities of biomaterialsby leveraging mechanics–geometry–biofunction relationships, which are beginning to shape the newly emergingfield of mechanobiomaterials. To profile this emerging field, this article aims to elucidate the fundamentalprinciples in modulating biological responses with material–tissue mechanical interactions, illustrate recentfindings on the relationships between material properties and biological responses, discuss the importance ofmathematical/physical models and numerical simulations in optimizing material properties and geometry, andoutline design strategies for mechanobiomaterials and their potential for tissue repair and regeneration. Giventhat the field of mechanobiomaterials is still in its infancy, this article also discusses open questions and challengesthat need to be addressed.

关键词： biomaterials geometry repair

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