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Recent Advances for Enhancing Drug Metabolizing Functions of Hepatocyte- like Cells Derived from Human Pluripotent Stem Cells 增强人多能干细胞衍生的肝细胞样细胞药物代谢功能的研究进展
Hanyang Medical Reviews Pub Date : 2015-11-01 DOI: 10.7599/HMR.2015.35.4.196
Jiyou Han, Jong Hoon Kim
{"title":"Recent Advances for Enhancing Drug Metabolizing Functions of Hepatocyte- like Cells Derived from Human Pluripotent Stem Cells","authors":"Jiyou Han, Jong Hoon Kim","doi":"10.7599/HMR.2015.35.4.196","DOIUrl":"https://doi.org/10.7599/HMR.2015.35.4.196","url":null,"abstract":"Clinical treatment for chronic liver failure using human embryonic stem cell (hESC) and human-induced pluripotent stem cell (hiPSC)-derived hepatocyte-like cells (HLCs) is considered a promising alternative method to organ transplantation. In addition to their use for treatment in liver failure, stem cell-derived HLCs have been considered for in vitro drug screening and toxicology researches [1]. Therefore, HLCs directly induced from hESCs have been intensively studied, resulting in a significant improvement in the efficiency of hepatic differentiation using human pluripotent stem cells. Albumin-positive HLCs can now be produced at the end of in vitro hepatic differentiation at levels up to 90% [2,3]. However, in spite of efforts to induce further maturation of HLCs derived from human pluripotent stem cells, the phenotype of most HLCs is more similar to fetal hepatocytes rather than fully mature hepatocytes. Critical inducing mature hepatocyte functions, such as phase I and II enzyme activity, tend to be significantly reduced in 2D-cultured HLCs (approximately <1% of human primary hepatocytes) [4,5]. Furthermore, under in vitro culture conditions, hepatobiliary transporter expression rapidly decreases [6], and most HLCs are spontaneously differentiate into various cell lineages, regardless of the differentiation protocol. Thus, at the final stage of hepatic differentiation, purification is needed to obtain highly homogenous HLCs. These key differences between HLCs and human primary hepatocytes result in limited use of HLCs as Hanyang Med Rev 2015;35:196-206 http://dx.doi.org/10.7599/hmr.2015.35.4.196","PeriodicalId":345710,"journal":{"name":"Hanyang Medical Reviews","volume":"117 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114968928","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
The Current Status of Directed Differentiation Technology 定向分化技术的现状
Hanyang Medical Reviews Pub Date : 2015-11-01 DOI: 10.7599/HMR.2015.35.4.215
Seung-Eun Lee, D. Choi
{"title":"The Current Status of Directed Differentiation Technology","authors":"Seung-Eun Lee, D. Choi","doi":"10.7599/HMR.2015.35.4.215","DOIUrl":"https://doi.org/10.7599/HMR.2015.35.4.215","url":null,"abstract":"This work was carried out with the support of “Cooperative Research Program for Agriculture Science & Technology Development (Project No. PJ0110022015)” Rural Development Administration, Republic of Korea.","PeriodicalId":345710,"journal":{"name":"Hanyang Medical Reviews","volume":"12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128527837","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
Induced Pluripotent Stem Cells: Next Generation Stem Cells to Clinical Applications 诱导多能干细胞:下一代干细胞的临床应用
Hanyang Medical Reviews Pub Date : 2015-11-01 DOI: 10.7599/HMR.2015.35.4.190
Ji-Man Cha, Sunhoo Park, Seung Bum Lee
{"title":"Induced Pluripotent Stem Cells: Next Generation Stem Cells to Clinical Applications","authors":"Ji-Man Cha, Sunhoo Park, Seung Bum Lee","doi":"10.7599/HMR.2015.35.4.190","DOIUrl":"https://doi.org/10.7599/HMR.2015.35.4.190","url":null,"abstract":"Induced pluripotent stem cells (iPSC) are specially manipulated cells from somatic cells by the introduction of four factors that are reprogrammed. The properties of iPSC are similar to embryonic stem cells (ESC) characteristic of self-renewal and pluripotency. The technology of reprogramming somatic cells to iPSC enables the generation of patient-specific cells that can be used as powerful tools for drug screening, in vitro models for human disease and autologous transplantation. The iPSC technology provides a priceless resource for regenerative medicine but there are still changing obstacles over the safety of iPSC in avoiding induction of tumorigenicity and maintaining high purity of re-differentiated cells from iPSC to produce more functional cells for cell therapy. A variety of methods to overcome the limitation of iPSC application applied in the clinical setting have been developed. In this review, we summarize the recent progress in iPSC generation and differentiation techniques to facilitate clinical application of iPSC with future potential in regenerative medicine.","PeriodicalId":345710,"journal":{"name":"Hanyang Medical Reviews","volume":"30 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127661302","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
Advanced Research on Stem Cell Therapy for Hepatic Diseases: Potential Implications of a Placenta-derived Mesenchymal Stem Cell-based Strategy 肝脏疾病干细胞治疗的最新研究:基于胎盘源性间充质干细胞策略的潜在意义
Hanyang Medical Reviews Pub Date : 2015-11-01 DOI: 10.7599/HMR.2015.35.4.207
G. Kim
{"title":"Advanced Research on Stem Cell Therapy for Hepatic Diseases: Potential Implications of a Placenta-derived Mesenchymal Stem Cell-based Strategy","authors":"G. Kim","doi":"10.7599/HMR.2015.35.4.207","DOIUrl":"https://doi.org/10.7599/HMR.2015.35.4.207","url":null,"abstract":"Stem cells are unique undifferentiated cells that have the potential for self-renewal activity while also possessing the ability to differentiate into multiple-lineages. They are categorized into embryonic stem cells (ESCs) and adult stem cells (ASCs), which include hematopoietic stem cells (HSCs) and non-hematopoietic stem cells (e.g. mesenchymal stem cells, or MSCs). ESCs that are reintroduced into blastocysts can participate in the development of all organs and tissues in the adult animal, confirming their intrinsic potency [1]. This demonstrated plasticity has made ESCs the benchmark against which stem cell potency is measured. Although ESCs have great potential, problems related to ethics, politics, and safety remain challenges to their future applications in regenerative medicine. Recently, there has been an explosion in the number of adult stem cells that have been isolated and characterized [2]. Every tissue or organ apparently contains a stem cell population; therefore, stem cells can be easily harvested, and stem cells with low immuHanyang Med Rev 2015;35:207-214 http://dx.doi.org/10.7599/hmr.2015.35.4.207","PeriodicalId":345710,"journal":{"name":"Hanyang Medical Reviews","volume":"41 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128782984","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: 5
New Horizons in Stem Cell Research 干细胞研究的新视野
Hanyang Medical Reviews Pub Date : 2015-11-01 DOI: 10.7599/HMR.2015.35.4.187
D. Choi
{"title":"New Horizons in Stem Cell Research","authors":"D. Choi","doi":"10.7599/HMR.2015.35.4.187","DOIUrl":"https://doi.org/10.7599/HMR.2015.35.4.187","url":null,"abstract":"generate injured tissues and organs in the body. Therefore, this special issue has been published to review the clinical implication of using various stem cell types (from pluripotent to adult including direct differentiated cells) to heal patients suffering from chronic human disorders such as cerebrovascular diseases, chronic liver diseases, cardiovascular disorders, musculoskeletal diseases, and fatal cancers. The emergence of human embryonic stem cell (ESC) lines is one of the most important achievements in the biological sciences during the previous century and has raised a broad scientific and social interest as it is believed embryonic stem cells can be utilized in the near future as a powerful source of material for cell transplantation in regenerative medicine. Studies with human ESC have enabled us to elucidate the gene expression patterns related to pluripotency and to initiate basic research allowing medical scientists to create induced pluripotent stem cells by several methods. Understanding genetic manipulation that can direct stem cells to develop into various lineages of terminally differentiated cells enable us directly to make differentiated cells from various cell sources. In terms of clinical application, adult stem cells including mesenchymal stem cells have become a central focus in the real world. The establishment of an outstanding research laboratory for stem cell research and regenerative medicine involves translational research including the development of Good Manufacturing Practice (GMP) and clean room facilities in companies and medical schools. Further development and the establishment of systems for the production of autologous adult stem cells for clinical usage increase our capabilities for treating patients who have suffered from chronic diseases.","PeriodicalId":345710,"journal":{"name":"Hanyang Medical Reviews","volume":"11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127972615","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
Adult Stem Cell Therapy in Chronic Liver Diseases 慢性肝病的成体干细胞治疗
Hanyang Medical Reviews Pub Date : 2015-11-01 DOI: 10.7599/HMR.2015.35.4.236
Y. Eom, S. Baik
{"title":"Adult Stem Cell Therapy in Chronic Liver Diseases","authors":"Y. Eom, S. Baik","doi":"10.7599/HMR.2015.35.4.236","DOIUrl":"https://doi.org/10.7599/HMR.2015.35.4.236","url":null,"abstract":"The transplantation of mesenchymal stem cells (MSCs) represents a potentially effective therapy for chronic liver diseases. The potential of MSCs in the treatment of chronic liver disease is based on their ability to differentiate into multiple cell types including hepatocytes, their immunosuppressive properties, and their ability to secrete various trophic factors. This potential has been investigated in clinical and pre-clinical studies. Although the therapeutic mechanisms of MSC transplantation are still not fully characterized, accumulating evidence has revealed that various trophic factors secreted by MSCs play key therapeutic roles in regeneration. These trophic factors not only reduce inflammation, apoptosis, and fibrosis in damaged tissues but also stimulate angiogenesis and tissue regeneration in the impaired liver. In this review, we summarize the basic and therapeutic properties of MSCs, their therapeutic mechanisms of action, and potential transplantation routes for the treatment of chronic liver disease. We also discuss several risks associated with the use of MSCs in therapy, such as their fibrogenic potential and capacity to promote pre-existing tumor cell growth.","PeriodicalId":345710,"journal":{"name":"Hanyang Medical Reviews","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122704088","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: 2
Current Concepts in Stem Cell Therapy for Cardiovascular Diseases: What We Know and Don't Know 干细胞治疗心血管疾病的当前概念:我们知道的和不知道的
Hanyang Medical Reviews Pub Date : 2015-11-01 DOI: 10.7599/HMR.2015.35.4.242
K. Jeon
{"title":"Current Concepts in Stem Cell Therapy for Cardiovascular Diseases: What We Know and Don't Know","authors":"K. Jeon","doi":"10.7599/HMR.2015.35.4.242","DOIUrl":"https://doi.org/10.7599/HMR.2015.35.4.242","url":null,"abstract":"Medical therapies and mechanical interventions for the treatment of myocardial infarction (MI) and ischemic heart failure have seen great progress. However, current therapies only slow the progression to heart failure, but do not stimulate regeneration to recover the loss of functional myocytes. Stem cell-based therapy is a novel modality that can potentially be used for the treatment of ischemic cardiac injury and heart failure wherein cardiac tissue is regenerated thereby improving cardiac function and reducing the morbidity and mortality of patients. Many preclinical and clinical trials have employed various types of stem cells including bone marrow-derived mononuclear cells, skeletal myoblasts, resident cardiac stem cells, mesenchymal stem cells, and endothelial progenitor cells, and these studies have suggested great potential for the clinical application of stem cell therapy for cardiac disease. Here we will review and summarize the current evidence indicating the potential of stem cell therapy, focusing on the clinical trials conducted to date.","PeriodicalId":345710,"journal":{"name":"Hanyang Medical Reviews","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116953492","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
Recent Advances in Skeletal Muscle Stem Cells for Duchenne Muscular Dystrophy Treatment 骨骼肌干细胞治疗杜氏肌营养不良的最新进展
Hanyang Medical Reviews Pub Date : 2015-11-01 DOI: 10.7599/HMR.2015.35.4.222
Jin Young Yang, Jaemin Jeong
{"title":"Recent Advances in Skeletal Muscle Stem Cells for Duchenne Muscular Dystrophy Treatment","authors":"Jin Young Yang, Jaemin Jeong","doi":"10.7599/HMR.2015.35.4.222","DOIUrl":"https://doi.org/10.7599/HMR.2015.35.4.222","url":null,"abstract":"About 50 years ago, the satellite cell was discovered through electron microscopic inspection of skeletal muscle. Satellite cells are mono-nucleated and located in the edge of the skeletal myofibers. These cells were imposed for their association with muscle regeneration. Satellite cells maintain dormant state in the mature muscle and are activated mitotically during muscle injuries, and finally differentiated to myoblasts. It contributes to the myofibrils resulting in muscle recovery from the injury [1]. Collins proved that satellite cells have both differentiation and self-renewal ability [2]. Sequentially, Kuang et al. established that the muscle stem cells achieve self-renewal through asymmetrical divisions. Also, satellite cells did not consist of only adult stem cells, rather both adult stem cells and committed progenitor cells [3]. Muscular dystrophies include many diseases, which have skeletal muscle wasting and limit mobility of patients. Among that, Duchenne muscular dystrophy (DMD), fragility of respiratory muscles and absence of dystrophin protein in the cardiac muscle results in respiratory or cardiac failure and early death [4]. The underlying pathogenesis is already investigated, but the treatment has not been established yet. However, research has accumulated these days and clinical trials are also being performed now. There are roughly four methods to research DMD treatments, 1) gene therapy replacing the mutated gene, 2) cell therapy which replace affected cells or using bone marrow-derived stem cells and mesoangioblasts, 3) repairing the endogenous gene using exon skipping, skipping premature termination, and 4) drug therapy which compensates for lack of dystrophin, promotes function in dystrophic muscle, improves muscle hypertrophy and minimizes muscle wasting, uses histone deacetylase inhibitors or NO-releasing anti-inflammatory drugs [5]. In this article, cell therapies in DMD are focused in a review and current clinical trials using cell therapy are introduced. Hanyang Med Rev 2015;35:222-228 http://dx.doi.org/10.7599/hmr.2015.35.4.222 pISSN 1738-429X eISSN 2234-4446","PeriodicalId":345710,"journal":{"name":"Hanyang Medical Reviews","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130478448","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: 2
Cancer Stem Cells: Biological Features and Targeted Therapeutics 癌症干细胞:生物学特征和靶向治疗
Hanyang Medical Reviews Pub Date : 2015-11-01 DOI: 10.7599/HMR.2015.35.4.250
Se Yong Song, Daekwan Seo
{"title":"Cancer Stem Cells: Biological Features and Targeted Therapeutics","authors":"Se Yong Song, Daekwan Seo","doi":"10.7599/HMR.2015.35.4.250","DOIUrl":"https://doi.org/10.7599/HMR.2015.35.4.250","url":null,"abstract":"Advance in stem cells (SCs) has become significant by the isolation of the tissue-specific SCs in a tissue, because it is the beginning of using SC utility for regenerative medicine. Likewise in SCs, a small subpopulation of cancer cells, named cancer stem cells (CSCs), also have similar properties. These properties include indefinite self-renewal potential and sharing similar signaling pathways with normal SCs, because the originality of CSCs is from the mutation of normal SCs. Hierarchically, CSCs in solid tumors may organize from the normal SCs in the highest cellular hierarchy of these cancer cells. The functional assay techniques to assess the differentiation frequency of normal SCs are similarly used in CSCs to sustain tumor growth and recurrence after therapy. In this review, we discuss the different parallels between adult SCs and CSCs in solid cancer disease and applications toward targeted therapy in use of molecular level on CSCs.","PeriodicalId":345710,"journal":{"name":"Hanyang Medical Reviews","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125516056","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: 2
Disaster Medical Assistance Team 灾难医疗援助小组
Hanyang Medical Reviews Pub Date : 2015-08-01 DOI: 10.7599/HMR.2015.35.3.152
K. Lee
{"title":"Disaster Medical Assistance Team","authors":"K. Lee","doi":"10.7599/HMR.2015.35.3.152","DOIUrl":"https://doi.org/10.7599/HMR.2015.35.3.152","url":null,"abstract":"A modern Disaster Medical Assistance Team (DMAT) is a group of professional and paraprofessional medical personnel organized to provide rapid-response medical care during a disaster situation. DMAT is a part of the disaster response system that acts as a trained, mobile, self-contained medical team in the acute phase of a disaster to provide necessary services such as triage, treatment, and transportation of injured patients in the devastated disaster area. The timeliness of DMAT response is critical to the administration of medical care and reduction of immediate mortality in disaster. While the number of members in a DMAT may vary between different nations. A small-scale DMAT is often composed of five to six people and there is good reason to consider this an effective unit for early disaster medical responses. An adequate structure and training system should be provided for Korean DMAT development in the near future.","PeriodicalId":345710,"journal":{"name":"Hanyang Medical Reviews","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123658245","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: 5
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