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基于微流控的仿生细胞封装

Science China Materials 2024年第8期67卷 2414-2426页

作者：王经琳黄丹青方壹乐任昊桢赵远锦 Division of Hepatobiliary and Transplantation Surgery Department of General SurgeryNanjing Drum Tower Hospital(The Affiliated Hospital of Nanjing University Medical School)Nanjing 210008China State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China

将细胞封装在生物材料中用于器官修复或疾病治疗是一个新兴领域.目前,微流控技术被用于精确控制封装细胞的数量、大小和支架结构.微流控技术提供了设计生物仿生形态的能力,增强封装细胞的活性和功能,从而提高疾病治疗的效果.本文报道了... 详细信息

将细胞封装在生物材料中用于器官修复或疾病治疗是一个新兴领域.目前,微流控技术被用于精确控制封装细胞的数量、大小和支架结构.微流控技术提供了设计生物仿生形态的能力,增强封装细胞的活性和功能,从而提高疾病治疗的效果.本文报道了微流控技术在仿生细胞封装方面的最新进展.我们首先简要概述了各种天然衍生的促进细胞功能的仿生结构,如受到细胞、植物、动物和自然反应启发的结构;之后讨论了基于微技术的最新细胞封装方法,并详细描述了相关过程;最后提出了仿生细胞封装在疾病治疗和临床应用中面临的挑战和未来方向.

关键词：微流控技术封装方法仿生结构仿生形态疾病治疗未来方向支架结构精确控制

Stimuli-Responsive Gene Delivery Nanocarriers for Cancer Therapy

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Nano-Micro Letters 2023年第3期15卷 299-331页

作者： Qingfei Zhang Gaizhen Kuang Wenzhao Li Jinglin Wang haozhen ren Yuanjin Zhao Department of Hepatobiliary Surgery The Affiliated Drum Tower Hospital of Nanjing University Medical SchoolHepatobiliary Institute of Nanjing UniversityNanjing 210008People’s Republic of China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhou 325001People’s Republic of China State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096People’s Republic of China Chemistry and Biomedicine Innovation Center Nanjing UniversityNanjing 210023People’s Republic of China

Gene therapy provides a promising approach in treating cancers with high efficacy and selectivity and few adverse ***,the development of functional vectors with safety and effectiveness is the intense focus for improving the delivery of nucleic acid drugs for gene *** this purpose,stimuli-responsive nanocarriers displayed strong potential in improving the overall efficiencies of gene therapy and reducing adverse effects via effective protection,prolonged blood circulation,specific tumor accumulation,and controlled release profile of nucleic acid ***,synergistic therapy could be achieved when combined with other therapeutic *** review summarizes recent advances in various stimuliresponsive nanocarriers for gene ***,the nanocarriers responding to endogenous stimuli including pH,reactive oxygen species,glutathione,and enzyme,etc.,and exogenous stimuli including light,thermo,ultrasound,magnetic field,etc.,are ***,the future challenges and prospects of stimuli-responsive gene delivery nanocarriers toward potential clinical translation are well *** major objective of this review is to present the biomedical potential of stimuli-responsive gene delivery nanocarriers for cancer therapy and provide guidance for developing novel nanoplatforms that are clinically applicable.

关键词： Stimuli-responsive Nanocarrier Gene therapy Gene delivery Cancer

双样本孟德尔随机化研究探讨肠道微生物与肝癌的关系

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中国临床研究 2024年第6期37卷 891-894,907页

作者：陈昱延任昊桢管文贤南京大学医学院附属鼓楼医院普通外科肝胆与肝移植外科江苏南京210008 南京大学医学院附属鼓楼医院普通外科江苏南京210008

目的通过双样本孟德尔随机化方法探讨221种肠道微生物与肝癌是否存在关联,为肝癌防治提供思路。方法使用IEU OpenGWAS数据库的肝癌数据(n=197611)作为结局数据,从一项大规模多种族基因组关联研究的元分析中获取肠道微生物数据(n=18340)... 详细信息

目的通过双样本孟德尔随机化方法探讨221种肠道微生物与肝癌是否存在关联,为肝癌防治提供思路。方法使用IEU OpenGWAS数据库的肝癌数据(n=197611)作为结局数据,从一项大规模多种族基因组关联研究的元分析中获取肠道微生物数据(n=18340)作为暴露数据,主要采用逆方差加权法进行分析,根据效应指标优势比(OR)和95%CI评估结果,同时使用留一法和异质性检验以及MR-PRESSO方法进行质量控制。结果颤螺菌属(Oscillibacter)丰度的提升,可以增加肝癌的患病概率(OR=1.411,95%CI:1.049~1.899,P=0.025)。留一法分析结果表明,该研究的结果稳定,并且未发现对结果产生强烈影响的工具变量。结果显示肠道微生物与肝癌之间存在正向的因果关系,并且可以消除异质性和水平基因多效性对因果效应估计所产生的影响。结论颤螺菌属丰度的提升,可以增加肝癌的患病概率。

关键词：肝癌肠道微生物颤螺菌属双样本孟德尔随机化公共基因组关联研究

Orthotopic implantable liver decellularized scaffold for acute liver failure

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再生工程(英文)

再生工程(英文) 2023年第1期4卷 12-19页

作者： Jinglin Wang Xueqian Qin Senzhe Xia Shujun Liu haozhen ren Department of Hepatobiliary Surgery the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolHepatobiliary Institute of Nanjing UniversityNanjing210008China

Decellularized scaffolds have an irreplaceable role in the development of tissue *** in this field are concentrated on shaping macro-scale constructs and maintaining blood ***,we establish a whole liver perfused decellularized scaffold cultured with hepatocytes for transplantable bioengineered liver *** to retained intact gross morphology of liver,geometric structure and biomechanical environment can support whole liver lobe ***,unremoved extracellular matrix(ECM)and vascular net-works can delivery continuous nutrient for cell *** on recellularized bioengineering liver scaffold,we have demonstrated its excellent hepatic functions when it orthotopic implanted in acute liver failure(ALF)rats,along with the prolonged survival rate and improved biochemical *** outstanding properties indicate that the orthotopic implantable liver scaffold has broad clinical application prospects in the treatment of ALF and other regeneration diseases.

关键词： Decellularized scaffolds Orthotopic implant Acute liver failure Tissue engineering Extracellular matrix

Transplantation of Mesenchymal Stem Cells Attenuates Acute Liver Failure in Mice via an Interleukin-4-dependent Switch to the M2 Macrophage Anti-inflammatory Phenotype

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Journal of Clinical and Translational Hepatology 2022年第4期10卷 669-679页

作者： Jinglin Wang Haoran Ding Jingchao Zhou Senzhe Xia Xiaolei Shi haozhen ren Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine Nanjing University of Chinese MedicineNanjingJiangsuChina Department of Hepatobiliary Surgery Affiliated Drum Tower Hospital of Nanjing Univer-sity Medical SchoolNanjingJiangsuChina Department of Hepatobiliary Surgery Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityJiangsuChina Department of Hepatobiliary Surgery Nanjing Drum Tower Hospital Clinical College of Jiangsu UniversityNanjingJiangsuChina

Background and Aims:Transplantation of mesenchymal stem cells(MSCs)derived from bone marrow(BM)is an alternative treatment of acute liver failure(ALF)mainly be-cause of the resulting anti-inflammatory *** is not known how MSCs regulate local immune responses and liver *** study explored the effects of MSCs on hepatic macrophages and the Wnt signaling pathway in ***:MSCs were isolated from BM aspirates of C57BL/6J mice,and transplanted in mice with ALF induced by D-galactosamine(D-Gal).The proliferation of hepato-cytes was assayed by immunohistochemical(IHC)staining of Ki-67 and proliferating cell nuclear antigen(PCNA).The levels of key proteins in the Wnt signaling pathway were assayed by western blotting and cytokines were determined enzyme-linked immunosorbent assays(ELISAs).A mac-rophage polarization assay characterized the M1/M2 *** potential role of interleukin-4(IL-4)in the biological ac-tivity of MSCs was determined by silencing of ***:Transplantation of allogeneic MSCs significantly attenuated D-Gal-induced hepatic inflammation and promoted liver *** transplantation significantly promoted a phenotypic switch from proinflamatory M1 macrophages to anti-inflammatory M2 macrophages,leading to significant Wnt-3a induction and activation of the Wnt signaling path-way in mice with D-Gal-induced *** the paracrine fac-tors secreted by MSCs(G-CSF,IL-6,IL-1 beta,IL-4,and IL-17A),IL-4 was specifically induced following transplantation in the ALF model *** silencing of IL-4 significantly ab-rogated the phenotypic switch to M2 macrophages and the protective effects of MSCs in both the ALF model mice and a co-culture model in an IL-4 dependent ***-sions:In vivo and in vitro studies showed that MSCs ame-liorated ALF through an IL-4-dependent macrophage switch toward the M2 anti-inflammatory *** findings may have clinical implications in that overexpression of IL-4 may enhance the therapeu

关键词： Acute liver failure Mesenchymal stem cells Interleukin 4 Macrophage Wnt signaling pathway

Acoustofluidics for cell patterning and tissue engineering

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Engineered Regeneration

Engineered Regeneration 2022年第4期3卷 397-406页

作者： Zhuhao Wu Meidie Pan Jinglin Wang Baojie Wen Ling Lu haozhen ren Institute of Translational Medicine The Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing210002China School of Medicine Zhejiang UniversityHangzhou310030China

Acoustofluidics has been a promising approach using sound waves to manipulate particles and actuate fluids in biomedical *** usually generates acoustic radiation force and acoustic streaming to initiate diffraction,reflection and interference,building up a pressure distribution to facilitate accurate manipulation of micro-or nano-scale particles and *** to its remarkable contact-free and biocompatible advantages,acoustoflu-idics has been used in high-throughput cell analysis,size-controllable organoid structures,and functional tissue *** enumerate the basic concepts and the sufficient research of acoustofluidics in precise patterning and tissue engineering in this review,including the design and function of four typical acoustofluidic devices,var-ious forms of cell patterning and 3D tissue ***,we outlined current challenges and future directions of acoustofluidics in biomedicine and tissue engineering.

关键词： Acoustofluidics Cell patterning Tissue engineering Disease models Engineered regeneration

Developing tissue engineering strategies for liver regeneration

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Engineered Regeneration 2022年第1期3卷 80-91页

作者： Jinglin Wang Danqing Huang Hang Yu Yi Cheng haozhen ren Yuanjin Zhao Department of Hepatobiliary Surgery Institute of Translational MedicineNanjing Drum Tower HospitalThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210002China State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)WenzhouZhejiang 325001China Institute for Stem Cell and Regeneration Chinese Academy of ScienceBeijing 100101China

The regenerative function of liver can be destroyed by viral infection,drug poisoning and tumorigenesis,resulting in irreversible *** approaches in promoting liver repair intend to replace liver transplantation,which is faced with a shortage of *** to the significant advantages in cell programming and bioscaf-fold engineering,liver tissue engineering is considered to be the most promising alternative for mimicking liver microstructure,maintaining hepatic function or implanting whole *** sources gradually develop from pri-mary hepatocytes,tumor cells,stem cell-induced cells to multiple cell coculture formats,spheroids and organoids,which have realized the improvement of cell function,overcome the problem of large-scale cell expansion and avoid the risk of immune ***,biocompatible materials are applied as cell carriers,and decel-lularized scaffolds and three-dimensional bioprinting liver pipeline structures are also used to accelerate cell colonization and *** enumerate sufficient research concerning liver tissue engineering in this re-view,including single and multiple cell sources,implantable and extracorporeal scaffold materials,and so on,providing critical conclusions and future implications of tissue engineering in liver regenerative applications.

关键词： Liver regeneration Scaffold Stem cells Bioartificial liver system Liver-on-a-chip

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训练免疫在相关疾病中的研究进展

南京医科大学学报（自然科学版） 2021年第11期41卷 1695-1701页

作者：苏可王经琳任昊桢施晓雷南京大学医学院附属鼓楼医院肝胆外科江苏南京210008

训练免疫(trained immunity,TI)是不依赖T、B细胞的,区别于传统固有免疫特征的一种记忆性固有免疫应答,在机体初次感染后对相同或不同病原体再次感染表现高反应性。训练免疫作为一种新兴的观点,具体机制涉及固有免疫、代谢及表观遗传之... 详细信息

训练免疫(trained immunity,TI)是不依赖T、B细胞的,区别于传统固有免疫特征的一种记忆性固有免疫应答,在机体初次感染后对相同或不同病原体再次感染表现高反应性。训练免疫作为一种新兴的观点,具体机制涉及固有免疫、代谢及表观遗传之间的交互作用。基于此,本文总结了脂多糖(lipopolysaccharide,LPS)、卡介苗(bacille calmette-guerin,BCG)、激素等刺激对单核/巨噬细胞、自然杀伤细胞等先天免疫细胞以及非经典免疫细胞的表观遗传和代谢修饰的影响,并探讨了调节训练免疫在炎症、神经系统疾病以及新冠肺炎等方面的作用。

关键词：训练免疫固有免疫免疫记忆代谢重组表观遗传重编程

机器人、腹腔镜以及开腹肝切除术治疗肝内胆管结石的对比研究

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南京医科大学学报（自然科学版） 2021年第1期41卷 82-87页

作者：王帅任昊桢汤宁张玉衡施晓雷南京大学医学院附属鼓楼医院肝胆外科江苏南京210008

目的:探讨比较机器人、腹腔镜、开腹肝切除术治疗肝内胆管结石的安全性和有效性。方法:回顾性分析2019年5月—2020年4月在南京大学医学院附属鼓楼医院肝胆外科接受达芬奇机器人辅助肝段切除手术治疗的肝内胆管结石患者23例,同时纳入腹... 详细信息

目的:探讨比较机器人、腹腔镜、开腹肝切除术治疗肝内胆管结石的安全性和有效性。方法:回顾性分析2019年5月—2020年4月在南京大学医学院附属鼓楼医院肝胆外科接受达芬奇机器人辅助肝段切除手术治疗的肝内胆管结石患者23例,同时纳入腹腔镜手术(20例)、开腹手术(25例)治疗的肝内胆管结石患者作为对照,比较3组患者基本临床信息、手术时间、失血量、输血情况、肝门阻断情况、术后住院时间、术后肛门排气时间、术后进食时间、下床活动时间、视觉模拟评分(visual analogue scale,VAS)、肝功能、并发症等情况。结果:机器人组手术时间与腹腔镜组相近,均长于开腹组;由于机器人装机消耗一定时间,去除装机时间以后,机器人组实际手术操作时间与开腹组相近。术中出血方面,机器人组出血量最少,腹腔镜组次之,开腹组最多。全肝门阻断方面,机器人组和腹腔镜组的肝门阻断比例明显低于开腹组。此外,机器人与腹腔镜在促进术后恢复方面整体优于开腹手术,包括术后住院时间更短、肛门通气更快、术后进食更早、下床活动更快以及VAS更低。3组患者的术后肝功能以及并发症发生率没有统计学差异。结论:机器人手术以及腹腔镜手术能够有效减少肝内胆管结石肝切除手术出血量,降低全肝门阻断率,促进术后恢复。尤其在缩短手术操作时间、降低出血量、加快术后出院方面,机器人手术明显优于腹腔镜手术。

关键词：肝内胆管结石肝切除术机器人手术