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Recent advances in multicellular human liver models 人类多细胞肝脏模型的最新进展
Brain Organoid and Systems Neuroscience Journal Pub Date : 2022-10-25 DOI: 10.51335/organoid.2022.2.e26
Seon Ju Mun, Jaeseo Lee, Yong-Moon Shin, Vincent Eun, Youngmi Ji, M. Son
{"title":"Recent advances in multicellular human liver models","authors":"Seon Ju Mun, Jaeseo Lee, Yong-Moon Shin, Vincent Eun, Youngmi Ji, M. Son","doi":"10.51335/organoid.2022.2.e26","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e26","url":null,"abstract":"The liver is the most important metabolic organ in the body. Model systems that recapitulate the complex organ structure and cell composition of the human liver are insufficient to study liver biology and to test toxicity and efficacy during new drug development. Recently established 3-dimensional liver models, including spheroids and organoids, organs-on-a-chip, bioprinting, and the decellularization/recellularization technique, have provided platforms that emulate the structural and functional characteristics of the human liver better than conventional 2-dimensional cell culture models and animal models. This review summarizes the architecture and cell compositions of human liver tissue, focusing on recent studies of multicellular human liver models that recapitulate in vivo-like physiologies with morphological and functional advances by the cellular communication of parenchymal and non-parenchymal cells. We discuss the applications, limitations, and future perspectives of advanced multicellular human liver models.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"73 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85706999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Toward brain organoid-based precision medicine in neurodegenerative diseases 基于脑器官的神经退行性疾病精准医学研究
Brain Organoid and Systems Neuroscience Journal Pub Date : 2022-10-24 DOI: 10.51335/organoid.2022.2.e21
Jong-Chan Park, I. Mook-Jung
{"title":"Toward brain organoid-based precision medicine in neurodegenerative diseases","authors":"Jong-Chan Park, I. Mook-Jung","doi":"10.51335/organoid.2022.2.e21","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e21","url":null,"abstract":"In recent years, the concept of precision medicine—an approach to developing personalized drugs for disease prevention or treatment—has emerged as an up-and-coming field in medical research. However, there are numerous limitations to applying this approach to the treatment of neurodegenerative diseases, such as Alzheimer disease, because of the invasiveness of obtaining human brain samples. Meanwhile, the development of human brain organoids has become one of the most powerful in vitro research tools because these organoids can be established from induced pluripotent stem cells or embryonic stem cells. In this review, we discuss how we can effectively utilize brain organoids for precision medicine research in conjunction with a variety of high-end techniques such as clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR-Cas9) genomic editing, integrative multi-omics analysis, 3D brain tissue clearing, and high-content screening confocal microscopy imaging systems. We herein provide new insights in order to materialize organoid-based precision medicine therapy and future directions.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88466466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Generation of human-induced pluripotent stem cell-derived adherent 3-dimensional skin hair-follicle organoids 人诱导多能干细胞衍生的贴壁三维皮肤毛囊类器官的生成
Brain Organoid and Systems Neuroscience Journal Pub Date : 2022-09-25 DOI: 10.51335/organoid.2022.2.e23
Mai Tran Thi Nhu, Ulziituya Batjargal, H. Song, Jin-Man Kim, I. Kwak, Byoung-San Moon
{"title":"Generation of human-induced pluripotent stem cell-derived adherent 3-dimensional skin hair-follicle organoids","authors":"Mai Tran Thi Nhu, Ulziituya Batjargal, H. Song, Jin-Man Kim, I. Kwak, Byoung-San Moon","doi":"10.51335/organoid.2022.2.e23","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e23","url":null,"abstract":"Regenerating hair follicles (HFs) is a critical medical need for patients who suffer from serious hair loss. To generate equivalent hair-bearing skin systems that could mimic the complexity of native tissues with pluripotent stem cells, floating culture has been employed as a standard method; however, it is still necessary to improve limitations such as the heterogeneity of organoids and the difficulty of handling them, which increases during long-term culture. Here, we devise a floating-adherent combinatory culture system to establish skin HF organoids from human-induced pluripotent stem cells (hiPSCs). Specifically, embryoid bodies were generated in a free-floating environment, followed by the induction process, which occurred in adherent conditions. With our approach, hair germ-like buds were shown to protrude and extend faster. After 100 days of culture, mature cystic skin organoids stratified to form the epidermis, dermis, and outer root sheath, as evident from quantitative polymerase chain reaction and immunohistochemistry analysis. Dermal condensate cells (Sox2+, PDGFRα+, P75+), which are the precursors of HFs, were detected together with HF stem cells (NFATC1+, LGR5+), putative bulge stem cells (LHX2+, KRT15+) and melanocytes (PMEL+). Notably, our constructed HFs could recapitulate the sensory function of native tissues, as illustrated by the formation of a network of sensory neurons and Schwann cells connecting towards HF cells and epidermal progenitors. In summary, our results demonstrate a new protocol for the simplified and efficient induction of skin HFs from hiPSCs, thereby contributing to research on optimizing HF growth and investigating novel therapeutic strategies to treat alopecia.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87076794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Methods to identify epithelial stem cells 鉴定上皮干细胞的方法
Brain Organoid and Systems Neuroscience Journal Pub Date : 2022-09-25 DOI: 10.51335/organoid.2022.2.e24
Youngtae Jeong
{"title":"Methods to identify epithelial stem cells","authors":"Youngtae Jeong","doi":"10.51335/organoid.2022.2.e24","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e24","url":null,"abstract":"Epithelial tissue is a tissue type that mainly covers the surfaces of the body and organs. Most epithelial tissues are composed of highly proliferative cells, necessitating robust stem cell activity. Epithelial tissue is also the most common site of cancers. Therefore, identifying epithelial stem cells and their self-renewal mechanisms is a prerequisite for promoting epithelial homeostasis, understanding cancer pathogenesis, and developing regenerative therapy and cancer prevention. Over the decades, diverse experimental techniques have been developed to identify epithelial stem cells in many organs and their self-renewal mechanisms from different angles. This review briefly introduces the various experimental methods used in stem cell identification, their rationales, and examples applying those tools to tissue stem cell identification.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"116 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74424019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Negative regulation of CDKN1A by the histone methyltransferase EHMT2 for cell growth in colorectal cancer 组蛋白甲基转移酶EHMT2对结直肠癌细胞生长的负调控CDKN1A
Brain Organoid and Systems Neuroscience Journal Pub Date : 2022-09-15 DOI: 10.51335/organoid.2022.2.e20
Kwangho Kim, Dae-Soo Kim, M. Son, Hyun-Soo Cho
{"title":"Negative regulation of CDKN1A by the histone methyltransferase EHMT2 for cell growth in colorectal cancer","authors":"Kwangho Kim, Dae-Soo Kim, M. Son, Hyun-Soo Cho","doi":"10.51335/organoid.2022.2.e20","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e20","url":null,"abstract":"The epigenetic regulation of oncogenes and tumor suppressor genes by histone methyltransferases is an important process for colon cancer growth and metastasis. Although various epigenetic modifiers have been recognized as attractive therapeutic targets for colon cancer treatment, alternative epigenetic regulation in colon cancer for reducing side effects and increasing the effectiveness of treatments has not been thoroughly explored. In this study, we identified CDKN1A as a direct target for EHMT2 by RNA-sequencing and found increased growth suppression via upregulation of CDKN1A by EHMT2 knockdown. In addition, using a 3-dimensional culture system for spheroid formation with an ultralow attachment plate, we confirmed EHMT2-related growth suppression and CDKN1A regulation. Thus, we suggest that EHMT2 may be a therapeutic target for colon cancer treatment, and an EHMT2 inhibitor should be developed for the effective treatment of colon cancer.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89508197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinical applications and optimization of patient-derived organoids in intestinal diseases 患者源性类器官在肠道疾病中的临床应用及优化
Brain Organoid and Systems Neuroscience Journal Pub Date : 2022-08-25 DOI: 10.51335/organoid.2022.2.e22
Tae Il Kim
{"title":"Clinical applications and optimization of patient-derived organoids in intestinal diseases","authors":"Tae Il Kim","doi":"10.51335/organoid.2022.2.e22","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e22","url":null,"abstract":"Since the first successful establishment of organoids from adult intestinal stem cells, organoid technology has rapidly developed. With advances in normal organoid technology, intestinal disorders, such as colorectal tumors and inflammatory bowel disease, have been major target diseases for patient-derived organoid (PDO) development. PDO biobanking for colorectal cancer has subsequently been developed, and some reports have shown the possibility of using PDO models to predict anticancer drug responses. However, to apply these models to real-world practice, we need more long-term clinical follow-up data from further large-scale PDO biobanks, as well as advanced technology for more rapid and efficient PDO establishment. In addition, in the field of regenerative medicine, the implantation of healthy intestinal PDOs to refractory tissue defects could be a new treatment strategy to accelerate the healing and repair of mucosal defects. This PDO technology could also be applied to inflammatory bowel diseases and serve as a very useful model for drug development via high-throughput screening of useful candidate drugs.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88392256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A brain metastasis model for breast cancer using human embryonic stem cell-derived cerebral organoids 利用人胚胎干细胞衍生的脑类器官建立乳腺癌脑转移模型
Brain Organoid and Systems Neuroscience Journal Pub Date : 2022-08-25 DOI: 10.51335/organoid.2022.2.e25
M. Choe, M. Lee
{"title":"A brain metastasis model for breast cancer using human embryonic stem cell-derived cerebral organoids","authors":"M. Choe, M. Lee","doi":"10.51335/organoid.2022.2.e25","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e25","url":null,"abstract":"Background: Breast cancer is a common cause of brain metastasis. Although breast cancer has relatively high survival rates, its survival rate after metastasis to the brain is lower. Conventional two-dimensional cell culture models and animal models are widely used in metastatic cancer research, and these models have tremendously contributed to the understanding of this disease. However, these models have some limitations, such as different physiological features and genetic backgrounds.Methods: We established a simple metastatic breast cancer model using human pluripotent stem cell-derived cerebral organoids (COs)—in this case, breast cancer cerebral organoids (BC-COs).Results: Using the BC-CO model, we induced the metastasis of MDA-MB-231 cells into COs by co-culture of cells with COs and compared the differences between adapted cancer cells in BC-COs and non-adapted cells. Our results showed that the proliferative capacity increased in adapted cells. Additionally, the expression levels of endothelial-mesenchymal transition markers and cancer stem cells were significantly higher in adapted cancer cells.Conclusion: We conclude that metastasis promotes the metastatic capacity of breast cancer cells. Our results also showed that the BC-CO model could be a novel tool for research on brain metastasis in breast cancer.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"2016 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78723764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Technical advances in pluripotent stem cell-derived and tumorigenic organoids 多能干细胞衍生和致瘤性类器官的技术进展
Brain Organoid and Systems Neuroscience Journal Pub Date : 2022-08-18 DOI: 10.51335/organoid.2022.2.e18
Suwon Kang, Eun Kyung Bong, Hyo-Min Kim, Tae-Young Roh
{"title":"Technical advances in pluripotent stem cell-derived and tumorigenic organoids","authors":"Suwon Kang, Eun Kyung Bong, Hyo-Min Kim, Tae-Young Roh","doi":"10.51335/organoid.2022.2.e18","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e18","url":null,"abstract":"Cell culture systems have been widely used to address fundamental questions in biology without sacrificing animals. Three-dimensional (3D) organoids provide more information on in vivo conditions than traditional culture systems because multiple cell types in organoids interact with each other in 3D structures. Despite extensive research and advances in the organoid field, some important limitations remain and need further consideration. In this review, we summarize how organoids are generated from pluripotent stem cells and describe the recent technical progress that has made organoids more similar to in vivo tissues for the application of organoids to modeling cancer. Lastly, we briefly discuss some limitations that have been raised in this field.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82939031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advanced human liver models for the assessment of drug-induced liver injury 用于评估药物性肝损伤的先进人肝模型
Brain Organoid and Systems Neuroscience Journal Pub Date : 2022-07-25 DOI: 10.51335/organoid.2022.2.e17
Seon Ju Mun, Jaeseo Lee, Yong-Moon Shin, M. Son
{"title":"Advanced human liver models for the assessment of drug-induced liver injury","authors":"Seon Ju Mun, Jaeseo Lee, Yong-Moon Shin, M. Son","doi":"10.51335/organoid.2022.2.e17","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e17","url":null,"abstract":"Drug safety issues continue to occur even with drugs that are approved after the completion of clinical studies. Drug-induced liver injury (DILI) is a major obstacle to drug development, because the liver is the primary site of drug metabolism, and injuries caused during this process are severe. Conventional in vitro human liver models, such as 2-dimensional hepatic cell lines, lack in vivo physiological relevance, and animal studies have limitations in the form of species differences and regulatory restrictions. To resolve this issue, an increasing number of 3-dimensional human liver systems, including organoids, are being developed. In this review, we provide an overview of recent assessments of DILI prediction, approaches for in vitro hepatotoxicity evaluation, and a variety of advanced human liver models. We discuss the advantages, limitations, and future perspectives of current human liver models for accurate drug safety evaluations.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91425349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A method for culturing patient-derived lung cancer organoids from surgically resected tissues and biopsy samples 一种从手术切除组织和活检样本中培养患者来源的肺癌类器官的方法
Brain Organoid and Systems Neuroscience Journal Pub Date : 2022-07-25 DOI: 10.51335/organoid.2022.2.e19
Y. R. Ko, Ji min Kim, Younsoo Kang, Minsuh Kim, S. Jang
{"title":"A method for culturing patient-derived lung cancer organoids from surgically resected tissues and biopsy samples","authors":"Y. R. Ko, Ji min Kim, Younsoo Kang, Minsuh Kim, S. Jang","doi":"10.51335/organoid.2022.2.e19","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e19","url":null,"abstract":"Cancer model systems that maintain the genetic and phenotypic characteristics of human cancers are crucial for the study of precision cancer medicine. In this respect, patient-derived cancer organoids have been developed as preclinical models of various human cancers, with significant advantages over previous cancer models including patient-derived xenografts and cell lines. We recently reported a culture system of patient-derived lung cancer organoids (LCOs) that retain the characteristics of patients’ tumors. Here, we describe a detailed protocol for establishing LCOs from surgically resected tumor tissues and endoscopic biopsy samples. This method improves the efficiency of setting up LCOs composed of pure cancer cells and describes an additional procedure for reconstructing LCOs after cryopreservation. We confirmed that stored LCOs had the ability to self-organize and retain the morphological and genetic characteristics of their parental tissues. They also maintained their responsive properties to certain anticancer drugs after thawing. In conclusion, our method efficiently generates LCOs that enable anticancer drug screening at the individual patient level.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81159186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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