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Fibrotic liver extracellular matrix induces cancerous phenotype in biomimetic micro-tissues of hepatocellular carcinoma model

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Hepatobiliary & Pancreatic Diseases International 2025年第1期24卷 92-103页

作者： Kosar Nouri Abbas Piryaei Homeyra Seydi Ibrahim Zarkesh Ibrahim Ghoytasi Bahare Shokouhian Mustapha Najimi Massoud Vosough Department of Developmental Biology University of Science and CultureACECR 14155-4364 TehranIran Department of Regenerative Medicine Cell Science Research CenterRoyan Institute for Stem Cell Biology and TechnologyACECR 14155-4364 TehranIran Department of Stem Cells and Developmental Biology Cell Science Research CenterRoyan Institute for Stem Cell Biology and TechnologyACECR 14155-4364 TehranIran Department of Biology and Anatomical Sciences School of MedicineShahid Beheshti University of Medical SciencesTehranIran Department of Tissue Engineering and Applied Cell Sciences School of Advanced Technologies in MedicineShahid Beheshti University of Medical SciencesTehranIran Department of Cell Engineering Cell Science Research CenterRoyan Institute for Stem Cell Biology and TechnologyACECR 14155-4364 TehranIran Department of Medical Biotechnology School of Advanced Technologies in MedicineTehran University of Medical SciencesTehranIran Laboratory of Pediatric Hepatology and Cell Therapy Institute of Experimental and Clinical Research(IREC)UCLouvainBrusselsBelgium Experimental Cancer Medicine Institution for Laboratory MedicineKarolinska InstituteStockholmSweden

Background: Despite considerable advancements in identifying factors contributing to the development of hepatocellular carcinoma(HCC), the pathogenesis of HCC remains unclear. In many cases, HCC is a consequence of prolonged liver fibrosis, resulting in the formation of an intricate premalignant microenvironment. The accumulation of extracellular matrix(ECM) is a hallmark of premalignant microenvironment. Given the critical role of different matrix components in regulating cell phenotype and function, this study aimed to elucidate the interplay between the fibrotic matrix and malignant features in HCC. Methods: Liver tissues from both control(normal) and carbon tetrachloride(CCl_(4))-induced fibrotic rats were decellularized using sodium dodecyl sulfate(SDS) and Triton X-100. The resulting hydrogel from decellularized ECM was processed into micro-particles via the water-in-oil emulsion method. Microparticles were subsequently incorporated into three-dimensional liver biomimetic micro-tissues(MTs) comprising Huh-7 cells, human umbilical vein endothelial cells(HUVECs), and LX-2 cells. The MTs were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS) assay at day 11, immunofluorescence staining, immunoblotting, and spheroid migration assay at day 14 after co-culture. Results: Fibrotic matrix from CCl4-treated rat livers significantly enhanced the growth rate of the MTs and their expression of CCND1 as compared to the normal one. Fibrotic matrix, also induced the expression of epithelial-to-mesenchymal transition(EMT)-associated genes such as TWIST1, ACTA2, MMP9, CDH2, and VIMENTIN in the MTs as compared to the normal matrix. Conversely, the expression of CDH1 and hepatic maturation genes HNF4A, ALB, CYP3A4 was decreased in the MTs when the fibrotic matrix was used. Furthermore, the fibrotic matrix increased the migration of the MTs and their secretion of alpha-fetoprotein. Conclusions: Our findings suggest a

关键词： Liver fibrosis Decellularized extracellular matrix Spheroid Epithelial-to-mesenchymal transition cell differentiation Hepatocellular carcinoma

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Surface engineering of lipid nanoparticles: targeted nucleic acid delivery and beyond

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Biophysics Reports 2023年第5期9卷 255-278页

作者： Yi Lin Qiang Cheng Tuo Wei State Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Department of Biomedical Engineering College of Future Technology Peking University Beijing Institute for Stem Cell and Regenerative Medicine University of Chinese Academy of Sciences

Harnessing surface engineering strategies to functionalize nucleic acid-lipid nanoparticles(LNPs) for improved performance has been a hot research topic since the approval of the first si RNA drug, patisiran, and two m RNA-based COVID-19 vaccines, BNT162b2 and m RNA-1273. Currently, efforts have been mainly made to construct targeted LNPs for organ-or cell-type-specific delivery of nucleic acid drugs by conjugation with various types of ligands. In this review, we describe the surface engineering strategies for nucleic acid-LNPs, considering ligand types, conjugation chemistries, and incorporation methods. We then outline the general purification and characterization techniques that are frequently used following the engineering step and emphasize the specific techniques for certain types of ligands. Next,we comprehensively summarize the currently accessible organs and cell types, as well as the other applications of the engineered LNPs. Finally, we provide considerations for formulating targeted LNPs and discuss the challenges of successfully translating the “proof of concept” from the laboratory into the clinic. We believe that addressing these challenges could accelerate the development of surfaceengineered LNPs for targeted nucleic acid delivery and beyond.

关键词： Surface engineering Targeted delivery Lipid nanoparticles Nucleic acid delivery

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Role of Hematopoietic cell Transplantation in Pediatric and Adult Hemophagocytic Lymphohistiocytosis—Remaining Unknowns and Challenges

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Hematology/Oncology Clinics of North America 2025年第3期39卷 645-660页

作者： Nikiforow, Sarah Duncan, Christine N. Department of Medicine Harvard Medical School Medical Oncology Stem Cell Transplantation Dana-Farber Cancer Institute Boston 02215 MA United States Department of Pediatrics Harvard Medical School Pediatric Stem Cell Transplant Program Dana-Farber Cancer Institute Boston 02215 MA United States

The main indication for allogeneic HSCT in children is primary/familial HLH but indications in adults are diverse, including malignancy-associated HLH. Matched related donors have historically been the preferred stem cell source (if not sharing predisposing genetics) followed closely by unrelated donors, but haploidentical transplants are proving feasible. Choice of conditioning regimen between myeloablative and reduced-intensity (RIC) involves trade-offs between early toxicity, particularly veno-occlusive disease, and additional cellular infusions to address graft failure or poor chimerism. Allogeneic HSCT for HLH is most successful when primary disease is under control, so coordination between initial/salvage therapy and transplant initiation is key.

关键词： Chimerism Conditioning Donor HLH Immunodeficiency stem cell transplant

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Interconnections between diabetic corneal neuropathy and diabetic retinopathy:diagnostic and therapeutic implications

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Neural Regeneration Research 2025年第8期20卷 2169-2180页

作者： Mingyi Yu Faith Teo En Ning Chang Liu Yu-Chi Liu Tissue Engineering and Stem Cell Group Singapore Eye Research InstituteSingapore Yong Loo Lin School of Medicine National University of SingaporeSingapore Department of Cornea and External Eye Disease Singapore National Eye CenterSingapore Ophthalmology and Visual Sciences Academic Clinical Program Duke-NUS Medical SchoolSingapore

Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes *** corneal neuropathy refers to the progressive damage of corneal *** retinopathy has traditionally been considered as damage to the retinal ***,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural *** retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular ***,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface *** studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic *** review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal *** also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.

关键词： cornea corneal nerves diabetes diabetic corneal neuropathy diabetic retinopathy retina

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Exploring the impact of pericentric inversion of chromosome 9 on fertility in sperm donors

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Asian Journal of Andrology 2024年第3期26卷 302-307页

作者： Qian Liu Wen-Jun Zhou Zeng-Hui Huang Xiu-Hai Huang Jian Wu Xi-Ren Ji Xue-Feng Luo Yu-Ling Tang Rui-Jun Wang Li-Qing Fan Chuan Huang Wen-Bing Zhu Institute of Reproductive and Stem Cell Engineering Basic Medicine CollegeCentral South UniversityChangsha 410013China Clinical Research Center for Reproduction and Genetics in Hunan Province Reproductive and Genetic Hospital of CITIC-XiangyaChangsha 410005China

Pericentric inversion of chromosome 9(inv[9])is a common chromosomal structural variant,but its impact on clinical outcomesremains *** screening criteria of sperm banks are rarely mentioned to individuals with inv(9).In this study,we evaluatedthe fertility of sperm donors with inv(9)who met eligibility criteria for sperm banks(inv[9]-eligible donors).From March 2004 toMay 2022,chromosomal analysis of 16124 sperm donors at CITIC-Xiangya Human Sperm Bank in Hunan Province(Changsha,China)found that 251(1.6%)had chromosome variations,with inv(9)being the most prevalent at 1.1%.All 169 inv(9)-eligibledonors were contacted to collect fertility outcome data,along with 206 eligible donors without inv(9)as *** addition,semen samples from inv(9)-eligible donors and eligible donors underwent assessments of sperm fluorescence in situ hybridization(FISH),mitochondrial membrane potential,DNA fragmentation index,acrosome integrity,reactive oxygen species(ROS),andsperm *** showed that inv(9)did not significantly increase reproductive risks *** detecting ROSlevel differences,the clinical impact may be *** study provides new data on the inv(9)population that can serveas a valuable reference for decision-making by sperm banks as well as for genetic counseling and clinical guidance for individualscarrying inv(9)variant.

关键词： male fertility pericentric inversion of chromosome 9 sperm bank sperm functional parameters

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Lin28a maintains a subset of adult muscle stem cells in an embryonic-like state

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细胞研究（英文版） 2023年第9期33卷 712-726页

作者： Peng Wang Xupeng Liu Ziyue Yao Yu Chen Lanfang Luo Kun Liang Jun-Hao Elwin Tan Min-Wen Jason Chua Yan-Jiang Benjamin Chua Shilin Ma Liping Zhang Wenwu Ma Shuqing Liu Wenhua Cao Luyao Guo Lu Guang Yuefan Wang He Zhao Na Ai Yun Li Chunwei Li Ruiqi Rachel Wang Bin Tean Teh Lan Jiang Kang Yu Ng Shyh Chang Institute of Zoology Chinese Academy of SciencesBeijingChina Beijing.Institute for Stem Cell and Regenerative Medicine Institute for Stem Cell and RegenerationChinese Academy of SciencesBeijingChina University of Chinese Academy of Sciences BeijingChina NUS Graduate School for Integrative Sciences and Engineering National University of SingaporeSingaporeSIngapore institute of Molecular and Cell Biology Genome Institute of SingaporeAgency for Science Technology and ResearchSingaporeSingapore Laboratory of Cancer Therapeutics Program in Cancer and Stem Cell BiologyDuke-National University of Singapore Medical SchoolSingaporeSingapore Laboratory of Cancer Epigenome Division of Medical ScienceNational Cancer Centre SingaporeSingaporeSingapore University of Chinese Academy of Sciences BeijingChina CAS Key Laboratory of Genome Sciences and Information Beijing Institute of GenomicsChinese Academy of SciencesBeijingChina Department of Clinical Nutrition Peking Union Medical College HospitalChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina Institute of Zoology Chinese Academy of SciencesBeijingChina Beijing.Institute for Stem Cell and Regenerative Medicine Institute for Stem Cell and RegenerationChinese Academy of SciencesBeijingChina Laboratory of Cancer Therapeutics Program in Cancer and Stem Cell BiologyDuke-National University of Singapore Medical SchoolSingaporeSingapore Laboratory of Cancer Epigenome Division of Medical ScienceNational Cancer Centre SingaporeSingaporeSingapore CAS Key Laboratory of Genome Sciences and Information Beijing Institute of GenomicsChinese Academy of SciencesBeijingChina

During homeostasis and after injury,adult muscle stem cells(MuSCs)activate to mediate muscle ***,much remains unclear regarding the heterogeneous capacity of MuSCs for self-renewal and ***,we show that Lin28a is expressed in embryonic limb bud muscle progenitors,and that a rare reserve subset of Lin28a+Pax7-skeletal MuSCs can respond to injury at adult stage by replenishing the Pax7+MuSC pool to drive muscle *** with adult Pax7+MuSCs,Lin28a+MuSCs displayed enhanced myogenic potency in vitro and in vivo upon *** epigenome of adult Lin28a+MuSCs showed resemblance to embryonic muscle *** addition,RNA-sequencing revealed that Lin28a+MuSCs co-expressed higher levels of certain embryonic limb bud transcription factors,telomerase components and the p53 inhibitor Mdm4,and lower levels of myogenic differentiation markers compared to adult Pax7+MuSCs,resulting in enhanced self-renewal and stress-response ***,conditional ablation and induction of Lin28a+MuSCs in adult mice revealed that these cells are necessary and sufficient for efficient muscle ***,our findings connect the embryonic factor Lin28a to adult stem cell self-renewal and juvenile regeneration.

关键词： Muscle stem cells Regeneration

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Dual-functional polyetheretherketone surface modification for enhanced osseointegration and antibacterial activity in pH-responsive manner

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Journal of Materials Science & Technology 2024年第33期200卷 129-140页

作者： Rui Ding Zhang Yuan Ke Wang Pandi Peng Jiaheng Liang Kun Wang Ke Lin Hanxue Wu Peng Li Frontiers Science Center for Flexible Electronics(FSCFE) Xi’an Institute of Flexible Electronics(IFE)Xi’an Institute of Biomedical Materials and Engineering(IBME)Northwestern Polytechnical University(NPU)Xi’an710072China Xi’an Key Laboratory of Stem Cell and Regenerative Medicine Institute of Medical Research Northwestern Polytechnical UniversityXi’an710072China

Polyetheretherketone(PEEK)has been recognized for its immense potential in hard tissue repair applications due to its mechanical properties resembling those of natural ***,the inherent bioinertness of pristine PEEK results in insufficient ***,implant-associated infection(IAI)has become a serious threat in orthopedic *** risks usually lead to implant loosening,delayed healing,and even the failure of implantation,hampering many clinical applications of *** this study,we present a facile strategy to endow PEEK implants with enhanced osseointegration and pH-responsive antibacterial ***,pristine PEEK was first treated with mixed acids to obtain a porous structure(referred to as SNPEEK),and then the metal-phenolic networks(MPN)coating was prepared using layer-by-layer(LbL)assembly consisting of Sr^(2+) and tannin acid(TA)(referred to as ST coating).The results demonstrated that the dual-functional PEEK displayed enhanced antibacterial activity in pH-responsive *** pH 7.4,the antibacterial ratios were 71.72%and 66.79%against Staphylococcus aureus(MSSA,ATCC 25,923)and methicillin-resistant Staphylococcus aureus(MRSA,ATCC BAA-40),***,at pH 5.5,the antibacterial activities significantly increased,resulting in killing ratios of 99.98%and 100%,***,the dual-functional PEEK promoted osteogenic differentiation of pre-osteoblasts(MC3T3-E1)and migration of human umbilical vascular endothelial cells(HUVECs).In addition,the dual-functional PEEK demonstrated effective anti-infection ability and desirable new bone formation ability in vivo compared to both pristine PEEK and SNPEEK ***,this study provides a promising strategy to endow PEEK implants with effective osseointegration and anti-infective ability,representing a prospective solution to address current clinical challenges associated with PEEK implants.

关键词： Polyetheretherketone Surface modification Metal-phenolic network pH-responsive Anti-infective Osseointegration

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IS607 TnpB is a hypercompact RNA-guided DNA endonuclease

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细胞研究（英文版） 2024年第7期34卷 473-474页

作者： Hui Yang Dinshaw J.Patel Key Laboratory of RNA Innovation Science and EngineeringShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghaiChina Structural Biology Program Memorial Sloan-Kettering Cancer CenterNew YorkNYUSA

The Zhiwei Huang lab report on a hypercompact IS607 TnpB protein that naturally co-occurs with the conserved RAGATH-18 RNA,thereby identifying a new family of compact RNA-guided DNA *** an IS607 TnpB-based approach for programmable genome editing in both Escher-ichia coli and human cells,combined with its structural and target-adjacent motif divergence from earlier reported IS200/IS605 TnpB systems,highlights the diversity of the non-Cas genome editor toolbox.

关键词： endonuclease hypercompact rna-guided tnpb

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A neurovascular unit-on-a-chip:culture and differentiation of human neural stem cells in a three-dimensional microfluidic environment

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Neural Regeneration Research 2022年第10期17卷 2260-2266页

作者： Wen-Juan Wei Ya-Chen Wang Xin Guan 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 Cell and Precision Medicine DalianLiaoning ProvinceChina

Biological studies typically rely on a simple monolayer cell culture,which does not reflect the complex functional characteristics of human tissues and organs,or their real response to external *** technology has advantages of high-throughput screening,accurate control of the fluid velocity,low cell consumption,long-term culture,and high *** combining the multipotential differentiation of neural stem cells with high throughput and the integrated characteristics of microfluidic technology,an in vitro model of a functionalized neurovascular unit was established using human neural stem cell-derived neurons,astrocytes,oligodendrocytes,and a functional microvascular *** model comprises a multi-layer vertical neural module and vascular module,both of which were connected with a syringe *** provides controllable conditions for cell inoculation and nutrient supply,and simultaneously simulates the process of ischemic/hypoxic injury and the process of inflammatory factors in the circulatory system passing through the blood-brain barrier and then acting on the nerve tissue in the *** in vitro functionalized neurovascular unit model will be conducive to central nervous system disease research,drug screening,and new drug development.

关键词： (neural)differentiation astrocyte blood-brain barrier brain microvascular endothelial cells central nervous system microfluidics neural stem cells neuron neurovascular unit oligodendrocyte organ-on-a-chip

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Positively charged patches:tonic for CAR fitness

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细胞研究（英文版） 2023年第5期33卷 331-332页

作者： Meraj H.Khan Jan Joseph Melenhorst Cell Therapy & Immuno-Engineering Program Center for ImmunoTherapy & Precision Immuno-OncologyLerner Research InstituteCleveland ClinicClevelandOHUSA

Tonic signaling is a constitutive low-level activation of chimeric antigen receptors(CARs)in the absence of tumor antigen and plays an imperative role in the CAR-T *** a recent paper published in cell Research,Chen et *** that the positively charged patches on the surface of the CAR antigen-binding domain regulate CAR tonic signaling and open a door to further optimization of improvements of CAR.

关键词： Immunology Tumour immunology

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