Nonintegrating Direct Conversion Using mRNA into Hepatocyte-Like Cells

Yoon, Sangtae,Kang, Kyojin,Cho, Young-duck,Kim, Yohan,Buisson, Elina Maria,Yim, Ji-Hye,Lee, Seung Bum,Ryu, Ki-Young,Jeong, Jaemin,Choi, Dongho Hindawi 2018 BioMed research international Vol.2018 No.-

<P>Recently, several researchers have reported that direct reprogramming techniques can be used to differentiate fibroblasts into hepatocyte-like cells without a pluripotent intermediate step. However, the use of viral vectors for conversion continues to pose important challenges in terms of genome integration. Herein, we propose a new method of direct conversion without genome integration with potential clinical applications. To generate hepatocyte-like cells, mRNA coding for the hepatic transcription factors Foxa3 and HNF4<I>α</I> was transfected into mouse embryonic fibroblasts. After 10-12 days, the fibroblasts converted to an epithelial morphology and generated colonies of hepatocyte-like cells (R-iHeps). The generated R-iHeps expressed hepatocyte-specific marker genes and proteins, including albumin, alpha-fetoprotein, HNF4<I>α</I>, CK18, and CYP1A2. To evaluate hepatic function, indocyanine green uptake, periodic acid-Schiff staining, and albumin secretion were assessed. Furthermore, mCherry-positive R-iHeps were engrafted in the liver of Alb-TRECK/SCID mice, and we confirmed FAH enzyme expression in Fah<SUP>1R</SUP>Tyr<SUP>c</SUP>/RJ models. In conclusion, our data suggest that the nonintegrating method using mRNA has potential for cell therapy.</P>

Formation of Functional Hepatocyte-Like Cells through Direct Conversion and Transplantation into Various Mice Models

( Sangtae Yoon ),( Kyojin Kang ),( Yohan Kim ),( Elina Maria Buisson ),( Chang Hee Lee ),( Ji-hye Yim ),( Jaemin Jeong ),( Dongho Choi ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: The incidence of liver disease is increasing worldwide. Liver transplantation is the only way to treat serious liver diseases. However, demand for transplants is increasing, while supply is very scarce. Therefore, many researchers are studying ways to replace liver transplantation. The most representative of these is cell therapy using ESCs and iPSCs. However, these are not available for clinical use because of the disadvantage that it may form teratoma in the body. Therefore we suggest other method that direct conversion technique produce generation of hepatocyte-like cells from fibroblasts with two liver-specific transcription factors. Methods: First generation of hepatocyte-like cells (miHeps) were produced by lentivirus infection for continuously expression in host genome during conversion. Second generation of hepatocyte-like cells (R-iHeps) were produced by mRNA transfection. NSG and Albumin-Treck mice were used for in vivo transplantation. Results: Directly converted hepatocyte-like cells can proliferate, split, store, re-seed, and mature with DMSO. And hepatocyte marker genes and protein expressions, albumin, AFP, etc., were increased in both cells, and albumin secretion in the media was much higher than fibroblasts. Also these cells were transplanted into liver injury model, jo2-treated NSG mice and Albumin-Treck mice, to confirm engraftment in liver. After transplant, miHeps and R-Heps can be detected in the liver under the fluorescence microscope. Conclusions: Directly converted hepatocyte-like cells can be useful for liver regeneration instead of ESCs and iPSCs-derived hepatocyte-like cells.

무선 릴레이-OFDM 시스템에서의 네트워크 코딩과 MIMO 기법의 결합 Capacity 성능 분석

윤지선(Jisun Yoon),이상태(Sangtae Lee),신지태(Jitae Shin) 한국통신학회 2011 한국통신학회 학술대회논문집 Vol.2011 No.2

네트워크 코딩과 MIMO 기법을 이용한 무선 릴레이-OFDM 시스템의 BER 성능 분석

윤지선(Jisun Yoon),이상태(Sangtae Lee),김현태(Hyuntai Kim),신지태(Jitae Shin) 한국통신학회 2011 한국통신학회 학술대회논문집 Vol.2011 No.2

Network coding 을 사용한 무선 릴레이 시스템에서 Adaptive Modulation 과 MIMO 결합 기법의 성능분석

윤지선(Jisun Yoon),이상태(Sangtae Lee),박진현(Jinhyun Park),신지태(Jitae Shin) 한국통신학회 2011 한국통신학회 학술대회논문집 Vol.2011 No.6

Carbon-free Mn-doped LiFePO₄ cathode for highly transparent thin-film batteries

Lee, HyunSeok,Kim, Sangtae,Parmar, Narendra Singh,Song, Jong-Han,Chung, Kyung-yoon,Kim, Kwang-Bum,Choi, Ji-Won Elsevier Sequoia 2019 Journal of Power Sources Vol. No.

<P><B>Abstract</B></P> <P>The search for transparent battery cathodes primarily focuses on patterned electrodes with feature sizes below the optical absorption limit. This significantly limits the electrode capacity, as a large electrode area remains unused to maintain transparency. Herein, we report transparent olivine LiFe<SUB>0.77</SUB>Mn<SUB>0.23</SUB>PO<SUB>4</SUB> thin-film electrodes discovered through high-throughput continuous-composition-spread sputtering. After investigating six different Mn doping ratios, we found the optimal Mn-doped olivine composition with an enhanced discharge capacity of 45.7 μA h/cm<SUP>2</SUP>∙μm without using excessive nanosized features or carbon coating. The thin-film electrode exhibits a clear redox activity for both Fe<SUP>3+/2+</SUP> and Mn<SUP>3+/2+</SUP>, resulting in an enhanced average voltage over LiFePO<SUB>4</SUB> composition. A 250-nm-thick film exhibits an optical transmittance of over 80% in the visible region. The results in this study demonstrates that transparent cathode thin films can be developed based on phospho-olivines via doping strategies with high-throughput continuous-composition-spread sputtering methods.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Exploration of carbon-free transparent LiFe<SUB>1-<I>x</I> </SUB>Mn<SUB> <I>x</I> </SUB>PO<SUB>4</SUB> thin films by CCS. </LI> <LI> The capacity of carbon-free LiFe<SUB>0.77</SUB>Mn<SUB>0.23</SUB>PO<SUB>4</SUB> thin films is 45.7 μA h/cm<SUP>2</SUP>∙μm. </LI> <LI> Transmittance of Carbon-free LiFe<SUB>0.77</SUB>Mn<SUB>0.23</SUB>PO<SUB>4</SUB> thin film exhibits 82%. </LI> <LI> Carbon-free LiFe<SUB>0.77</SUB>Mn<SUB>0.23</SUB>PO<SUB>4</SUB> is suitable for transparent thin film batteries. </LI> </UL> </P>

Chemical Derived Patient-Specific Hepatic Stem Cells from Various Patients

( Kyojin Kang ),( Yohan Kim ),( Sangtae Yoon ),( Elina Maria Buisson ),( Changhee Lee ),( Ji-hye Yim ),( Jaemin Jeong ),( Dongho Choi ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Hepatocyte like cells can be derived from many different sources of stem cells including induced pluripotent stem cells, embryonic stem cells or directly converted cells. These Methods: are well developed, however, some problems such as tumor formation, low functionality and differentiation ratio as well as genomic variation are yet to be solved. Methods: We have developed a method using two small molecules and no ectopic gene expression to develop patient-specific hepatic stem cells (hCdH) from primary hepatocytes. Of interest, from 52 patients healthy and diseased patient livers, we were able to generate hCdH. Results: Among the 52 patients, significant differences in fibrosis were observed with 4.17% and 52% in the normal and diseased group respectively. The harvested hepatocytes ratio (number of cells/the liver weight) also differed with a mean of 5.9x10⁶ in normal livers and 1.1x10⁶ in diseased livers. In normal livers ALP ranged from 66 to 95 U/L whilst there was a significant increase in the ALP level of diseased livers ranging from 80 to 174 U/L. Through the evaluation of different platforms such as generation and differentiation ratio, hepatic marker expression and functionality of these hCdHs, we were able to find the most significant difference in the statistical analysis between the generation of CdH in healthy and diseased livers and the level of ALP(alkaline phosphatase). Through FACS analysis we were also able to find the stemness marker NPB24-B3 obtained from embryonic stem cells as a characteristic of CdH and sorted 36.2% of the cells accordingly. Conclusions: Although the CdH characteristics vary, it was possible to generate CdH from all patients. We therefore suggest that the functional state and generation efficiency of CdH are related to patient liver condition. In further studies, we plan to use the CdH marker to sort the cells obtained from the patients to allow for homogeneous population.

Reprogramming of Human Hepatocytes into Bi-Potent Hepatic Progenitor Cells Using Cocktail of Small Mole-cules and Growth Factor

( Yohan Kim ),( Kyojin Kang ),( Sangtae Yoon ),( Elina Maria Buisson ),( Chang Hee Lee ),( Ji-hye Yim ),( Jaemin Jeong ),( Dongho Choi ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Cell-based regenerative medicine can provide valuable options for end-stage patients with liver disease by solving and considering the lack of donor shortage through gene and/or stem cell therapy. Despite much progress in isolation and prolonged growth of bipotent progenitor cells with regenerative capacity from terminally differentiated mouse hepatocytes, expansion of the adult human hepatocytes remains a major challenge. Methods: We report using two small molecules and growth factors to successfully produce patient-specific hepatic progenitor cells from healthy and diseased human hepatocytes. Results: After three days of treatment small molecule in the presence of growth factor, a key driver of hepatic progenitor cell activity, triggered expansion of small polygonal cells, which co-expressed known hepatic progenitor cells and lineage specific marker genes. These chemically derived human hepatic progenitor cells (hCdHs) could self-renew for at least 10 passages while retaining phenotype, normal karyotype and potential to differentiate into functional hepatocytes and biliary epithelial cells in vitro. A next-generation sequencing confirmed a high degree of molecular similarity between hCdHs and human hepatoblasts. Upon intrasplenic transplantation into immunocompromised mice with a diseased liver, hCdHs effectively repopulated and restored. Conclusions: In conclusion, hCdHs provide a safe novel tool that permits expansion and genetic manipulation of patient-specific hepatic progenitor cells to study regeneration and repair of diseased liver.

콘셉트 수용도 평가를 통한 전략적 기술 구현의 사례 연구 ; 디럭스 유모차 디자인 개발 중심으로

선섭희 ( Suphee Sun ),윤기훈 ( Kihoon Yoon ),변상태 ( Sangtae Byun ) 한국산업디자이너협회(한국인더스트리얼디자인학회) 2016 산업디자인학연구 Vol.10 No.4

본 연구에서는 유아 시장의 지속 성장 확대와 수입 유모차의 비합리적 유통구조 배경으로 합리적인 소비를 지향하는 보육자의 니즈를 충족하고자 기획 단계에서부터 디자인 주도적으로 관여하여 디럭스 유모차 신제품 개발을 진행하였다. 이에 기존 유모차 시장에서 차별화를 위한 전략으로 디럭스 유모차의 요람스윙과 하이체어의 전략적 기능을 도출하고 실현 가능한 기술구조를 개발하였다. 연구의 방법은 국내외 브랜드 조사를 통해 기본 기능과 추가 기능을 분류하고 비참여 관찰 조사를 통해 사용자 관점에서 필요한 전략적 기능을 도출하고, 해당 기능의 구조 아이디어를 제시한 다음, 기능의 구체적 구현을 위해 기구설계가 진행되었다. 기능 콘셉트를 실제 구현하기 위해 기업관계자, 디자이너, 설계자의 밀착 유기적 공조를 통해 진행되었으며, 이는 마케팅과 생산, 사용자의 경험과 만족도, 전략적 기능의 동작 구현을 위한 기구설계 등을 모두 충족하고자 함이다. 마지막으로 구체화한 전략적 기능을 기반으로 디럭스 유모차 시제품을 제작한 후, FGI를 시행하여 신제품의 수용도 조사와 전략적 기능의 사용성을 평가하였다. 수요도 조사는 신제품과 신제품의 전략적 기능에 대한 선호도 중심으로 시행하였으며, 사용성 평가는 전략적 기능에 대한 조작 용이성, 조작행동 유동성, 기억 용이성, 동작 만족도를 평가하였다. 이에 본 연구를 통해 디자인 중심의 사고를 통하여 신제품에 대한 소비자 만족과 새로운 라이프스타일 선도는 물론, 기업제품이 고가의 수입 유모차 대체 효과를 이루고 지속 성장의 기반 마련을 기대한다. In this study, we developed a new deluxe stroller with design- driven from the planning stage to meet the needs of parents who are aiming rational consumption, on the background of continued growth and expansion of baby product market and unreasonable distribution structure of imported strollers. The progress of this study is as follows. First, we classify the basic features and additional features of the stroller through the domestic and international brand research. And by carrying out non-participant observation research, we derived the key functions required from the user's point of view. Next, we derived ideas about the structure of the function and proceed to the mechanical design to implement specific functions. Implementing process was proceeding through organic coordination of corporate representatives, designers, mechanical designers. This is intended to meet all of the needs of marketing and production, practical implementation of the strategic functions, and user’s satisfaction. Finally, we have produced a prototype based on the mechanical design and we verified the new functionality by evaluating the user acceptance and usability such as satisfaction with new features, ease of operation, behavior affordance and memory simplicity by user investigation. Thus, in the wake of this study, we expect that design-driven product development approach will improve customer satisfaction, lead new life-style of users, replace expensive imported products as domestic products and lay the foundation for sustainable growth of SMEs.

시공간도표에 기초한 특수상대론 시각화 자료 개발 및 적용 효과

권진영 ( Jinyoung Kwon ),윤여원 ( Yeowon Yoon ),최광규 ( Kwangkyu Choi ),박상태 ( Sangtae Park ) 한국현장과학교육학회 2020 현장과학교육 Vol.14 No.1

본 연구의 목적은 2009년 개정 교육과정에서 도입되어 현재까지 고등학교 교과서에 수록된 현대 물리학의 하나인 특수상대성이론의 기본 개념을 고등학생들이 이해하도록 도울 수 있는 시각화 자료를 설계하고, 수업에서 그 효과를 분석하는 것이다. 교과서의 전통적 방법으로 수업이 진행된 직후 실험집단과 통제집단 학생들에게 사전검사를 실시하였고, 이후 실험집단과 통제집단 학생들에게 빛 원 시각화 자료를 이용한 수업과 교과서에 소개된 전통적 수업을 각각 적용하고 동일한 문항으로 사후검사를 실시한 후 통계 프로그램을 이용하여 시각화 자료의 효과를 알아보았다. 시간 지연과 길이 수축을 이해하는데 있어 빛 원은 학업성취도를 높일 수 있는 효율적인 시각화 자료라 할 수 있다. 즉 특수상대론에 의해 나타나는 현상을 학습하는데 있어 관찰자에 따라 시간을 빛 원으로 표현하는 활동이 시간 지연과 길이 수축의 개념이해에 긍정적인 역할을 한 것으로 판단된다. The purpose of this study is to design the visualization materials which can help high school students understand the basic concepts of special relativity, one of the modern physics newly included in high school text books for the revised curriculum in 2009, and to analyze the effect of them in classes. After the traditional classes, both of experimental and control group had pre-test of basic concepts on special relativity the experimental group was presented with the concept of special relativity by using light circle visualization materials, and the control group was taught by using traditional teaching which is faithful to the content of textbooks. Then, the posttest same items with pre-test as post-test was given to both of them, and finally the effect of light circle visualization materials was analyzed. Consequently, the visualization materials using light circle showed significant achievement in time dilation and length contraction than using traditional teaching which is faithful to the content of textbooks. In conclusion, since the light circle visualization materials are effective in teaching time dilation and length contraction, the materials can be presented to help the students to better understand the basic concepts of special relativity who might have difficulty in understanding through traditional teaching which is faithful to the content of textbooks.