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Biofabrication of size-controlled liver microtissues incorporated with ECM-derived microparticles to prolong hepatocyte function

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Bio-Design and Manufacturing 2021年第4期4卷 790-805页

作者： Zahra Heydari Ibrahim Zarkesh Mohammad-Hossein Ghanian Mahdokht HAghdaei Svetlana Kotova Ensieh Zahmatkesh Zahra Farzaneh Abbas Piryaei Iman Akbarzadeh Anastasia Shpichka Roberto Gramignoli Peter Timashev Hossein Baharvand Massoud Vosough Department of Developmental Biology University of Science and CultureACECR14155-4364 TehranIran Department of Regenerative Medicine Cell Science Research CentreRoyan Institute for Stem Cell Biology and TechnologyACECR14155-4364 TehranIran Department of Stem Cells and Developmental Biology Cell Science Research CenterRoyan Institute for Stem Cell Biology and TechnologyACECR14155-4364 TehranIran Department of Cell Engineering Cell Science Research CenterRoyan Institute for Stem Cell Biology and TechnologyACECR14155-4364 TehranIran Transplant Research Center Shiraz University of Medical Sciences71936-13311 ShirazIran N.N.Semenov Federal Research Center for Chemical Physics Russian Academy of SciencesMoscow 117977Russia Department of Biology and Anatomical Sciences School of MedicineShahid Beheshti University of Medical Sciences14155-4364 TehranIran Department of Tissue Engineering and Applied Cell Sciences School of Advanced Technologies in MedicineShahid Beheshti University of Medical Sciences14155-4364 TehranIran Institute for Regenerative Medicine Sechenov UniversityMoscow 117977Russia Division of Pathology Department of Laboratory MedicineKarolinska Institute17177 StockholmSweden

Multicellular microtissues of primary human hepatocytes(PHHs)co-cultured with other supporting cell types are a promis-ing model for drug screening and toxicological ***,these liver microtissues(LMs)rapidly lose their functions during ex vivo ***,in order to mimic the cellular and structural hepatic microenvironment,we co-cultured PHHs with human mesenchymal stromal cells(MSCs)and human umbilical vein endothelial cells(HUVECs)in the presence of cell-sized microparticles(MPs)derived from liver extracellular matrix(LEMPs).The microwell culture platform enabled biofabrication of size-controlled multicellular microtissues(PHH:HUVEC:MSC=3:2:1)with efficient LEMP incorporation(about 70%at a 2:1 ratio of cells:MP).The biofabricated liver microtissues(BLMs)were cultured ex vivo for 14 days and compared to the cell-only LM in terms of gene and protein expression,functional activity,cytochrome P450(CYP450)enzyme inducibility,and drug *** results supported superior hepatic-related gene expression,functional activity,and polarity for PHH in BLM compared to ***450 enzyme inducibility and dose-responsive sensitivity to toxic drugs were significantly higher in the BLM *** conclusion,microtissue engineering by incorporation of tissue-specific microparticles within a multicellular microtissue can offer some advantages for drug discovery studies and cell transplantation *** the near future,this approach could generate a scalable platform of several functional biofabricated microtissues representing different organs.

关键词： Liver microtissue Hepatocyte maintenance Microparticles Decellularized tissue Drug screening

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Generation and characterization of stable pig pregastrulation epiblast stem cell lines

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细胞研究（英文版） 2022年第4期32卷 383-400页

作者： Minglei Zhi Jinying Zhang Qianzi Tang Dawei Yu Shuai Gao Dengfeng Gao Pengliang Liu Jianxiong Guo Tang Hai Jie Gao Suying Cao Zimo Zhao Chongyang Li Xiaogang Weng Mengnan He Tianzhi Chen Yingjie Wang Keren Long Deling Jiao Guanglei Li Jiaman Zhang Yan Liu Yu Lin Daxin Pang Qianqian Zhu Naixin Chen Jingjing Huang Xinze Chen Yixuan Yao Jingcang Yang Zicong Xie Xianya Huang Mengxin Liu Ran Zhang Qiuyan Li Yiliang Miao Jianhui Tian Xingxu Huang Hongsheng Ouyang Bofeng Liu Wei Xiei Qi Zhou Hongjiang Wei Zhonghua Liu Caihong Zheng Mingzhou Li Jianyong Han State Key Laboratory of Agrobiotechnology College of Biological SciencesChina Agricultural UniversityBeijingChina Institute of Animal Genetics and Breeding College of Animal Science and TechnologySichuan Agricultural UniversityChengduSichuanChina State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Institute for Stem Cell and Regenerative Medicine Chinese Academy of SciencesBeijingChina Beijing Institute for Stem Cell and Regenerative Medicine BeijingChina Key Laboratory of Animal Genetics College of Animal Science and TechnologyChina Agricultural UniversityBeijingChina State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan Yunnan Agricultural UniversityKunmingYunnanChina State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Animal Science and Technology College Beijing University of AgricultureBeijingChina Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province College of Life ScienceNortheast Agricultural UniversityHarbinHeilongjiangChina School of Life Science and Technology ShanghaiTech UniversityShanghaiChina Jilin Provincial Key Laboratory of Animal Embryo Engineering College of Animal SciencesJilin UniversityChangchunJilinChina Institute of Stem Cell and Regenerative Biology College of Animal Science and Veterinary MedicineHuazhong Agricultural UniversityWuhanHubeiChina Center for Stem Cell Biology and Regenerative Medicine MOE Key Laboratory of BioinformaticsTHU-PKU Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijingChina Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciencesand China National Center for BioinformationBeijingChina

Pig epiblast-derived pluripotent stem cells are considered to have great potential and broad prospects for human therapeutic model development and livestock *** ongoing attempts since the 1990s,no stably defined pig epiblast-derived stem cell line has been ***,guided by insights from a large-scale single-cell transcriptome analysis of pig embryos from embryonic day(E)0 to E14,specifically,the tracing of pluripotency changes during epiblast development,we developed an in vitro culture medium for establishing and maintaining stable pluripotent stem cell lines from pig E10 pregastrulation epiblasts(pgEpiSCs).Enabled by chemical inhibition of WNT-related signaling in combination with growth factors in the FGF/ERK,JAK/STAT3,and Activin/Nodal pathways,pgEpiSCs maintain their pluripotency transcriptome features,similar to those of E10 epiblast cells,and normal karyotypes after more than 240 passages and have the potential to differentiate into three germ ***,ultradeep in situ Hi-C analysis revealed functional impacts of chromatin 3D-spatial associations on the transcriptional regulation of pluripotency marker genes in *** practice,we confirmed that pgEpiSCs readily tolerate at least three rounds of successive gene editing and generated cloned gene-edited live *** findings deliver on the long-anticipated promise of pig pluripotent stem cells and open new avenues for biological research,animal husbandry,and regenerative biomedicine.

关键词： Developmental biology Pluripotent stem cells Life Sciences general cell Biology

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Preparation of Temperature-Sensitive Hollow Fiber Membrane and Its Detection as a cell Carrier 29th

Preparation of Temperature-Sensitive Hollow Fiber Membrane a...

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29th International Conference on Computational and Experimental engineering and Sciences, ICCES 2023

作者： Wang, Hao Sun, Yiyi Wang, Jingwen Yuan, Yuhuang Cheng, Yuen Yee Li, Xiangqin Song, Kedong State Key Laboratory of Fine Chemicals Dalian R&D Center for Stem Cell and Tissue Engineering Dalian University of Technology Dalian116024 China Faculty of Science Institute for Biomedical Materials and Devices University of Technology Sydney SydneyNSW2007 Australia

ISBN: (纸本)9783031449468

NIPAAm has been widely used in cell culture and non-destructive desorption in recent years because it can change its surface configuration by changing temperature. In this study, NIPAAm was grafted onto the surface of the HFMs with cerium ammonium nitrate (CAN) as the initiator to prepare the thermosensitive HFMs. This material was used as a cell carrier for temperature sensitivity and biocompatibility assays to achieve non-destructive harvesting of cells from the surface of the HFMs. The morphology showed that poly (n-isopropylacrylamide) (PNIPAAm) was successfully grafted onto the HFMs. The results of water contact angle at different temperatures showed that the prepared samples have good temperature sensitivity. At 37 °C, PC12 cells adhered to and diffused well on the surface of PNIPAAm-g-HFMs. After cooling to 20 °C, the cells fell off the surface of the membrane in sheet form and retain more extracellular matrix proteins. PNIPAAm-g-HFMs in this study have good biocompatibility and can be better used as cell carriers in cell culture in vitro. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2024.

关键词： cells

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ERMAP is a B7 family-related molecule that negatively regulates T cell and macrophage responses

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cellular & Molecular Immunology 2021年第8期18卷 1920-1933页

作者： Min Su Yujun Lin Cheng Cui Xiaohong Tian Laijun Lai Department of Human Histology and Embryology School of Basic Medical SciencesStem Cell and Tissue Engineering Research CentreGuizhou Medical UniversityGuiyangGuizhouChina Department of Allied Health Sciences University of ConnecticutStorrsCTUSA University of Connecticut Stem Cell Institute University of ConnecticutStorrsCTUSA

T cell activation and tolerance are tightly regulated by costimulatory and coinhibitory molecules.B7 family members play a crucial role in regulating immune *** this study,we identified erythroid membrane-associated protein(ERMAP)as a novel T cell inhibitory *** shares significant sequence and structural homology with existing B7 family members in its extracellular *** ERMAP protein is expressed on the cell surface of resting and activated antigen-presenting cells(APCs)and in some tumor *** putative ERMAP receptor is expressed on activated CD4 and CD8 T cells and *** mouse and human ERMAP-IgG2a Fc(ERMAP-Ig)fusion proteins inhibit T cell functions in *** of ERMAP-Ig protein ameliorates autoimmune diseases,including experimental autoimmune encephalomyelitis and type 1 diabetes,in ***-ERMAP antibody enhances macrophage phagocytosis of cancer cells in ***,administration of an anti-ERMAP antibody inhibits tumor growth in mice likely by blocking the inhibitory effects of ERMAP on T cells and *** results suggest that therapeutic interaction with the ERMAP inhibitory pathway may represent a novel strategy for treating patients with autoimmune disease or cancer.

关键词： T cells T cell inhibitory molecules autoimmunity EAE

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An Adjuvant Micelle-Based Multifunctional Nanosystem for Tumor Immunotherapy by Remodeling Three Types of Immunosuppressive cells

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ACS Nano 2024年第4期18卷 3134-3150页

作者： Meng, Siyu Du, Huiping Li, Xiang Zheng, Xinmin Zhao, Pan Yuan, Zhang Huang, Shaohui Zhao, Yanli Dai, Liangliang Xi’an Key Laboratory of Stem Cell and Regenerative Medicine Institute of Medical Research Northwestern Polytechnical University Xi’an710072 China School of Life Science Northwestern Polytechnical University Xian710072 China School of Life Sciences University of Chinese Academy of Sciences Beijing101499 China School of Chemistry Chemical Engineering and Biotechnology Nanyang Technological University 21 Nanyang Link Singapore637371 Singapore

Immunotherapy is restricted by a complex tumor immunosuppressive microenvironment (TIM) and low drug delivery efficiency. Herein, a multifunctional adjuvant micelle nanosystem (PPD/MPC) integrated with broken barriers and re-education of three classes of immune-tolerant cells is constructed for cancer immunotherapy. The nanosystem significantly conquers the penetration barrier via the weakly acidic tumor microenvironment-responsive size reduction and charge reversal strategy. The detached core micelle MPC could effectively be internalized by tumor-associated macrophages (TAMs), tumor-infiltrating dendritic cells (TIDCs), and myeloid-derived suppressor cells (MDSCs) via mannose-mediated targeting endocytosis and electrostatic adsorption pathways, promoting the re-education of immunosuppressive cells for allowing them to reverse from pro-tumor to antitumor phenotypes by activating TLR4/9 pathways. This process in turn leads to the remodeling of TIM. In vitro and in vivo studies collectively indicate that the adjuvant micelle-based nanosystem not only relieves the intricate immune tolerance and remodels TIM via reprogramming the three types of immunosuppressive cells and regulating the secretion of relevant cytokines/immunity factors but also strengthens immune response and evokes immune memory, consequently suppressing the tumor growth and metastasis. © 2024 American Chemical Society.

关键词： Tumors

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Corrigendum to ‘Diels-Alder-based IPN hydrogels with tunable mechanical and protein release properties for tissue engineering’[Int. J. Biol. Macromol. Volume 306, Part 4, May 2025, 141779] (International Journal of Biological Macromolecules (2025) 306(P4), (S014181302502330X), (10.1016/***.2025.141779))

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International Journal of Biological Macromolecules 2025年 308卷 142810页

作者： Segujja, Farouk Duruksu, Gokhan Eren, Elif Beyza Isayeva, Aygun Yazir, Yusufhan Erdem, Ahmet Department of Biomedical Engineering Faculty of Technology Kocaeli University Kocaeli41001 Turkey Department of Stem Cell Institute of Health Sciences Kocaeli University Kocaeli41001 Turkey Center for Stem Cell and Gene Therapies Research and Practice Kocaeli University Kocaeli41001 Turkey

Ahmet Erdem is recognized as the corresponding author of this article, an administrative adjustment that does not affect its scientific content. The authors would like to apologise for any inconvenience caused. ©...

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Dip-Printed Microneedle Motors for Oral Macromolecule Delivery

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Research 2022年第3期2022卷 177-187,I0009页

作者： Xiaoxuan Zhang Guopu Chen Lijun Cai Lu Fan Yuanjin Zhao Department of Rheumatology and Immunology Nanjing Drum Tower HospitalSchool of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhou 325001China Institute for Stem Cell and Regeneration Chinese Academy of ScienceBeijing 100101China

Micromotors have demonstrated values in drug delivery,and recent attempts focus on developing effective approaches to generate functional micromotors to improve this ***,with the integration of microfluidic droplet printing and wettability-induced drawing photolithography,we present an innovative spatiotemporal serial multistep dip-printing strategy to generate novel independent microneedle motors(IMNMs)for orally delivering macromolecular *** the strategy combines the advantages of the hydrophilic wettability,extension effects,and capillary effects,the IMNMs with an oblate basement and a needle-shaped head or a core-shell structured multicomponent head can be created by simply printing pregel droplets layer by layer,following with simultaneous wiredrawing and *** to the polarized magnetic particles in the bottom basement and the rapidly dissolvable polymers as the middle basement,the resultant IMNMs can respond to magnetic fields,move to desired places under a magnet,penetrate tissue-like substrates,induce head-basement separation,and leave only the needles for cargo *** on these features,we have demonstrated that these IMNMs can deliver insulin via intestinal tracts to realize effective blood glucose control of diabetic rabbit *** results indicate the practical values and bright future of the dip-printing stratagem and these IMNMs in clinical applications.

关键词： needle printing rabbit

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Three-dimensional breast cancer tumor models based on natural hydrogels:a review

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第9期25卷 736-755页

作者： Yan SHU Bing LI Hailin MA Jiaqi LIU Yuen Yee CHENG Xiangqin LI Tianqing LIU Chuwei YANG Xiao MA Kedong SONG State Key Laboratory of Fine Chemicals Dalian R&D Center for Stem Cell and Tissue EngineeringDalian University of TechnologyDalian116024China Institute for Biomedical Materials and Devices Faculty of ScienceUniversity of Technology SydneySydneyNSW2007Australia Emergency Center The Second Hospital of Dalian Medical UniversityDalian116023China Department of Anesthesia The First Affiliated Hospital of Dalian Medical UniversityDalian116011China

Breast cancer is the most common cancer in women and one of the deadliest cancers *** to the distribution of tumor tissue,breast cancer can be divided into invasive and non-invasive *** cancer cells in invasive breast cancer pass through the breast and through the immune system or systemic circulation to different parts of the body,forming metastatic breast *** resistance and distant metastasis are the main causes of death from breast *** on breast cancer has attracted extensive attention from *** vitro construction of tumor models by tissue engineering methods is a common tool for studying cancer mechanisms and anticancer drug *** tumor microenvironment consists of cancer cells and various types of stromal cells,including fibroblasts,endothelial cells,mesenchymal cells,and immune cells embedded in the extracellular *** extracellular matrix contains fibrin proteins(such as types Ⅰ,Ⅱ,Ⅲ,Ⅳ,Ⅵ,and Ⅹ collagen and elastin)and glycoproteins(such as proteoglycan,laminin,and fibronectin),which are involved in cell signaling and binding of growth *** current traditional two-dimensional(2D)tumor models are limited by the growth environment and often cannot accurately reproduce the heterogeneity and complexity of tumor tissues in ***,in recent years,research on three-dimensional(3D)tumor models has gradually increased,especially 3D bioprinting models with high precision and *** with a 2D model,the 3D environment can better simulate the complex extracellular matrix components and structures in the tumor ***-dimensional models are often used as a bridge between 2D cellular level experiments and animal *** matrix,gelatin,sodium alginate,and other natural materials are widely used in the construction of tumor models because of their excellent biocompatibility and non-immune ***,we review various natural scaffold materials and con

关键词： Breast cancer Tumor microenvironment 3D tumor model Decellularized extracellular matrix Natural scaffold materials

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Neuroregeneration and functional recovery after stroke: advancing neural stem cell therapy toward clinical application

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Neural Regeneration Research 2021年第1期16卷 80-92页

作者： Yang Jiao Yu-Wan Liu Wei-Gong Chen Jing Liu Stem Cell Clinical Research Center National Joint Engineering LaboratoryRegenerative Medicine CenterThe First Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina Dalian Innovation Institute of Stem Cells and Precision Medicine DalianLiaoning ProvinceChina

Stroke is a main cause of death and disability *** ability of the brain to selfrepair in the acute and chronic phases after stroke is minimal;however,promising stem cell-based interventions are emerging that may give substantial and possibly complete recovery of brain function after *** animal models and clinical trials have demonstrated that neural stem cells(NSCs)in the central nervous system can orchestrate neurological repair through nerve regeneration,neuron polarization,axon pruning,neurite outgrowth,repair of myelin,and remodeling of the microenvironment and brain *** with other types of stem cells,NSCs have unique advantages in cell replacement,paracrine action,inflammatory regulation and *** review summarizes NSC origins,characteristics,therapeutic mechanisms and repair processes,then highlights current research findings and clinical evidence for NSC *** results may be helpful to inform the direction of future stroke research and to guide clinical decision-making.

关键词： brain central nervous system cognitive impairment neurological function plasticity recovery regeneration stem cells stroke

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Lipid nanoparticles for mRNA therapy: recent advances in targeted delivery

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Life Medicine 2022年第1期1卷 21-23页

作者： Tuo Wei Wei Tao Qiang Cheng State Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101 China Institute for Stem Cell and Regeneration Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China Center for Nanomedicine and Department of Anesthesiology Brigham and Women’s Hospital Harvard Medical School Boston Massachusetts 02115 United States Department of Biomedical Engineering College of Future Technology Peking University Beijing 100871 China

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