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Genome-edited rabbits:Unleashing the potential of a promising experimental animal model across diverse diseases

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Zoological Research 2024年第2期45卷 253-262页

作者： Yang Han Jiale Zhou Renquan Zhang Yuru Liang Liangxue Lai Zhanjun Li Key Laboratory of Zoonosis Research Ministry of EducationCollege of Animal ScienceJilin UniversityChangchunJilin 130062China CAS Key Laboratory of regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineSouth China Institute for Stem Cell Biology and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouGuangdong 510530China Guangzhou regenerative medicine and Health Guang Dong Laboratory(GRMH-GDL) GuangzhouGuangdong 510005China Institute for stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China

Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene *** field of genome modification in rabbits has progressed ***,recent advancements,particularly in CRISPR/Cas9-related technologies,have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases,including cardiovascular disorders,immunodeficiencies,agingrelated ailments,neurological diseases,and ophthalmic *** models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to *** review aims to summarize the novel gene-editing approaches currently available for rabbits and present the applications and prospects of such models in biomedicine,underscoring their impact and future potential in translational medicine.

关键词： Genome editing Animal model Rabbit CRISPR/Cas9 Genetic diseases

CD9 role in proliferation, rejuvenation, and therapeutic applications

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Genes & Diseases 2024年第3期11卷 95-97页

作者： Sai Priyanka Kodam Neda Baghban Mujib Ullah Institutefor Immunityand Transplantation Stem Cell Biology and Regenerative MedicineSchool of MedicineMolecular Medicine Department of MedicineStanford UniversityPaloAltoCA94304USA

The CD9 gene,also known as the Tspan29 gene,codes for a protein called CD9,which is a member of the tetraspanin family of transmembrane proteins.^(1) The CD9 protein is involved in various cellular processes,including cell proliferation,differentiation,adhesion,and migration.^(1,2) CD9 has also been found to play a role in the regulation of stem cell proliferation and differentiation.

关键词： migration. therapeutic CD9

One-step cell biomanufacturing platform:porous gelatin microcarrier beads promote human embryonic stem cell-derived midbrain dopaminergic progenitor cell differentiation in vitro and survival after transplantation in vivo

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Neural Regeneration Research 2024年第2期19卷 458-464页

作者： Lin Feng Da Li Yao Tian Chengshun Zhao Yun Sun Xiaolong Kou Jun Wu Liu Wang Qi Gu Wei Li Jie Hao Baoyang Hu Yukai Wang 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 National stem cell Resource Center Chinese Academy of SciencesBeijingChina Savaid Medical School University of Chinese Academy of SciencesBeijingChina Beijing Institute for stem cell and regenerative medicine BeijingChina State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina

Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s *** of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s ***,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation ***,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor *** beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in ***,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell ***,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.

关键词： axonal integrity cell cryopreservation cellular environment cellular niche cell replacement therapy dopaminergic progenitors human pluripotent stem cell mechanical damage neuronal cell delivery Parkinson’s disease small-aperture gelatin microcarriers

Organoids as preclinical models of human disease:progress and applications

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Medical Review 2024年第2期4卷 129-153页

作者： Baodan Chen Cijie Du Mengfei Wang Jingyi Guo Xingguo Liu CAS Key Laboratory of regenerative Biology Joint School of Life SciencesGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou Medical UniversityGuangzhouChina Guangdong Provincial Key Laboratory of stem cell and regenerative medicine Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative MedicineChina-New Zealand Joint Laboratory on Biomedicine and HealthCUHK-GIBH Joint Research Laboratory on Stem Cells and Regenerative MedicineGIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research CentreInstitute for Stem Cell and RegenerationGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouChina University of Chinese Academy of Sciences BeijingChina Innovation centre for Advanced Interdisciplinary medicine The Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina centre for regenerative medicine and Health Hong Kong Institute of Science&InnovationChinese Academy of SciencesHong Kong SARChina

In the field of biomedical research,organoids represent a remarkable advancement that has the potential to revolutionize our approach to studying human diseases even before clinical *** are essentially miniature 3D models of specific organs or tissues,enabling scientists to investigate the causes of diseases,test new drugs,and explore personalized medicine within a controlled laboratory *** the past decade,organoid technology has made substantial progress,allowing researchers to create highly detailed environments that closely mimic the human *** organoids can be generated from various sources,including pluripotent stem cells,specialized tissue cells,and tumor tissue *** versatility enables scientists to replicate a wide range of diseases affecting different organ systems,effectively creating disease replicas in a laboratory *** exciting capability has provided us with unprecedented insights into the progression of diseases and how we can develop improved *** this paper,we will provide an overview of the progress made in utilizing organoids as preclinical models,aiding our understanding and providing a more effective approach to addressing various human diseases.

关键词： organoids human disease regenerative medicine drug screening tumor

Identification and characterization of human hematopoietic mesoderm

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Science China(Life Sciences) 2024年第2期67卷 320-331页

作者： Yuqi Wen Jingjing Zhao Runqing Zhang Fan Liu Xiaoyuan Chen Dan Wu Mengge Wang Cuicui Liu Pei Su Panpan Meng Yiyue Zhang Xin Gao Lu Wang Hongtao Wang Jiaxi Zhou State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Tianjin Institutes of Health Science Tianjin 301600China CAMS Center for stem cell medicine PUMC Department of Stem Cell and Regenerative MedicineTianjin 300020China Division of cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhou 510006China

The embryonic mesoderm comprises heterogeneous cell subpopulations with distinct lineage *** is unclear whether a bias for the human hematopoietic lineage emerges at this early developmental *** this study,we integrated single-cell transcriptomic analyses of human mesoderm cells from embryonic stem cells and embryos,enabling us to identify and define the molecular features of human hematopoietic mesoderm(HM)cells biased towards hematopoietic *** discovered that BMP4 plays an essential role in HM specification and can serve as a marker for HM ***,BMP4 acts as a downstream target of HDAC1,which modulates the expression of BMP4 by deacetylating its *** of HDAC significantly enhances HM specification and promotes subsequent hematopoietic cell *** conclusion,our study identifies human HM cells and describes new mechanisms for human hematopoietic development.

关键词： hematopoietic mesoderm human pluripotent stem cells human embryos BMP4 HDAC1

乳酸化修饰参与调控DNA损伤修复和癌细胞化疗敏感性

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Science Bulletin 2024年第9期69卷 1185-1187页

作者：刘子超黄奕乐刘兴国 CAS Key Laboratory of regenerative Biology Joint School of Life SciencesGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou Medical UniversityGuangzhou 510530China centre for regenerative medicine and Health Hong Kong Institute of Science&InnovationChinese Academy of SciencesHong Kong 999077China Guangdong Provincial Key Laboratory of stem cell and regenerative medicine Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative MedicineChina-New Zealand Joint Laboratory on Biomedicine and HealthCUHK-GIBH Joint Research Laboratory on Stem Cells and Regenerative MedicineGIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research CentreInstitute for Stem Cell and RegenerationGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China University of Chinese Academy of Sciences Beijing 100049China

The phenomenon in which cells prefer glycolysis to oxidative phosphorylation with increased lactate production is known as the Warburg effect and is found prevalent in cancer cells and pluripotent stem cells [1]. In addition to being an intermediate metabolite of glycolysis, lactate has been reported as a signal involved in multiple important biological processes, such as innate immunity [2], the cell cycle [3], hippocampal neurogenesis [4].

关键词：化疗敏感性 immunity DNA损伤修复

Placenta-derived mesenchymal stem cells attenuate secondary brain injury after controlled cortical impact in rats by inhibiting matrix metalloproteinases

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BIOcell 2024年第1期48卷 149-162页

作者： PING YANG YUANXIANG LAN ZHONG ZENG YAN WANG HECHUN XIA Department of Neurosurgery School of Clinical MedicineNingxia Medical UniversityYinchuanChina Key Laboratory of Ningxia stem cell and regenerative medicine General Hospital of Ningxia Medical UniversityYinchuanChina Department of Neurosurgery Xi’an International Medical Center HospitalXi’anChina

Background:As a form of biological therapy,placenta-derived mesenchymal stem cells(PDMSCs)exhibit considerable promise in addressing the complex pathological processes of traumaticbrain injury(TBI)due to their multi-target and multi-pathway mode of ***&Methods:This study investigates the protective mechanisms and benefits of PDMSCs in mitigating the effects of controlled cortical impact(CCI)in rats and glutamate-induced oxidative stress injury in HT22 cells in *** primary objective is to provide evidence supporting the clinical application of ***:In the in vivo arm of our investigation,we observed a swift elevation of matrix metalloproteinase-9(MMP-9)in the proximal cortex of injured brain tissues after ***,distinguished by their heightened expression of metalloproteinase tissue inhibitors-1 and-2(TIMP-1 and TIMP-2):were intravenously administered via the caudal *** intervention yielded significant reductions in the permeability of the blood-brain barrier(BBB):the extent of brain edema,the levels of inflammatory cytokines IL-1βand TNF-αin damaged brain tissue,and the activation status of microglia in CCI-afflicted *** the realm of in vitro experiments,PDMSC-conditioned media demonstrated substantial reductions in mortality rates and cleaved caspase-3 levels in glutamate-induced HT22 cells compared with conventional ***,this advantage was negated upon the introduction of neutralizing antibodies targeting TIMP-1 and ***:Collectively,our findings underscore the potential of PDMSCs in alleviating oxidative stress injury and secondary brain injury in the pathological process of TBI.

关键词： Traumatic brain injury Mesenchymal stem cells Oxidative stress Matrix metalloproteinases

Engineering pluripotent stem cells with synthetic biology for regenerative medicine

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Medical Review 2024年第2期4卷 90-109页

作者： Yihuan Mao Siqi Wang Jiazhen Yu Wei Li State Key Laboratory of stem cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Key Laboratory of Organ Regeneration and Reconstruction Chinese Academy of SciencesBeijingChina Beijing Institute for stem cell and regenerative medicine BeijingChina University of Chinese Academy of Sciences BeijingChina State Key Laboratory of stem cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Key Laboratory of Organ Regeneration and Reconstruction Chinese Academy of SciencesBeijing 100101China Beijing Institute for stem cell and regenerative medicine Beijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Pluripotent stem cells(PSCs),characterized by self-renewal and capacity of differentiating into three germ layers,are the programmable building blocks of ***-derived cells and multicellular systems,particularly organoids,exhibit great potential for regenerative ***,this field is still in its infancy,partly due to limited strategies to robustly and precisely control stem cell behaviors,which are tightly regulated by inner gene regulatory networks in response to stimuli from the extracellular *** receptors and genetic circuits are powerful tools to customize the cellular sense-and-response process,suggesting their underlying roles in precise control of cell fate decision and function ***,we review the progress and challenges needed to be overcome in the fields of PSC-based cell therapy and multicellular system generation,***,we summarize several well-established synthetic biology tools and their applications in PSC ***,we highlight the challenges and perspectives of harnessing synthetic biology to PSC engineering for regenerative medicine.

关键词： pluripotent stem cell regenerative medicine PSC-based cell therapy multicellular systems synthetic biology

Temporal and spatial regulation of biomimetic vascularization in 3D-printed skeletal muscles

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Bio-Design and Manufacturing 2024年第5期7卷 597-610页

作者： Minxuan Jia Tingting Fan Tan Jia Xin Liu Heng Liu Qi Gu Key Laboratory of Organ Regeneration and Reconstruction State Key Laboratory of Membrane BiologyInstitute of ZoologyChinese Academy of SciencesBeijing 100101China Beijing Institute for stem cell and regenerative medicine Beijing 100101China University of Chinese Academy of Sciences Beijing 100049China State Key Laboratory of stem cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Department of Orthopaedics Beijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China

In the intricate skeletal muscle tissue,the symbiotic relationship between myotubes and their supporting vasculature is pivotal in delivering essential oxygen and *** study explored the complex interplay between skeletal muscle and endothelial cells in the vascularization ofmuscle *** harnessing the capabilities of three-dimensional(3D)bioprinting and modeling,we developed a novel approach involving the co-construction of endothelial and muscle cells,followed by their subsequent *** findings highlight the importance of the interaction dynamics between these two cell ***,introducing endothelial cells during the advanced phases of muscle differentiation enhanced myotube ***,it stimulated the development of the vascular network,paving the way for the early stages of vascularized skeletal muscle *** methodology proposed in this study indicates the potential for constructing large-scale,physiologically aligned skeletal ***,it highlights the need for exploring the delicate equilibrium and mutual interactions between muscle and endothelial *** on the multicell-type interaction model,we can predict promising pathways for constructing even more intricate tissues or organs.

关键词： Skeletal muscle Vascularization 3D bioprinting cell interaction