Comparison of molecular profiles of human mesenchymal stem cells derived from bone marrow, umbilical cord blood, placenta and adipose tissue

HEO, JUNE SEOK,CHOI, YOUJEONG,KIM, HAN-SOO,KIM, HYUN OK UNKNOWN 2016 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.37 No.1

<P>Mesenchymal stem cells (MSCs) are clinically useful due to their capacity for self-renewal, their immunomodulatory properties and tissue regenerative potential. These cells can be isolated from various tissues and exhibit different potential for clinical applications according to their origin, and thus comparative studies on MSCs from different tissues are essential. In this study, we investigated the immunophenotype, proliferative potential, multilineage differentiation and immunomodulatory capacity of MSCs derived from different tissue sources, namely bone marrow, adipose tissue, the placenta and umbilical cord blood. The gene expression profiles of stemness-related genes [octamer-binding transcription factor 4 (<I>OCT4</I>), sex determining region Y-box (<I>SOX)2</I>, <I>MYC</I>, Krüppel-like factor 4 (<I>KLF4</I>), <I>NANOG</I>, <I>LIN28</I> and <I>REX1</I>] and lineage-related and differentiation stage-related genes [<I>B4GALNT1 (GM2/GS2 synthase)</I>, inhibin, beta A (<I>INHBA</I>), distal-less homeobox 5 (<I>DLX5</I>), runt-related transcription factor 2 (<I>RUNX2</I>), proliferator-activated receptor gamma (<I>PPARG</I>), CCAAT/enhancer-binding protein alpha (<I>C/EBPA</I>), bone morphogenetic protein 7 (<I>BMP7</I>) and <I>SOX9</I>] were compared using RT-PCR. No significant differences in growth rate, colony-forming efficiency and immunophenotype were observed. Our results demonstrated that MSCs derived from bone marrow and adipose tissue shared not only <I>in vitro</I> trilineage differentiation potential, but also gene expression profiles. While there was considerable interdonor variation in <I>DLX5</I> expression between MSCs derived from different tissues, its expression appears to be associated with the osteogenic potential of MSCs. Bone marrow-derived MSCs (BM-MSCs) significantly inhibited allogeneic T cell proliferation possibly via the high levels of the immunosuppressive cytokines, <I>IL10</I> and <I>TGFB1</I>. Although MSCs derived from different tissues and fibroblasts share many characteristics, some of the marker genes, such as <I>B4GALNT1</I> and <I>DLX5</I> may be useful for the characterization of MSCs derived from different tissue sources. Collectively, our results suggest that, based on their tri-lineage differentiation potential and immunomodulatory effects, BM-MSCs and adipose tissue-derived MSCs (A-MSCs) represent the optimal stem cell source for tissue engineering and regenerative medicine.</P>

COVID-19 치료 및 진단을 위한 Exosome의 임상적 적용

June Seok HEO 대한임상검사과학회 2024 대한임상검사과학회지(KJCLS) Vol.56 No.1

엑소좀은 나노 크기의 세포외 소포체로 핵산, 단백질, 지질 등다양한 생리활성 물질을 함유하고 있다. 엑소좀의 생리활성 물질들은 주변 세포나 조직으로 전달될 수 있을 뿐만 아니라 기원된 세포의 고유 특정 물질들을 지니고 있기 때문에 엑소좀 유래물질들은 진단 및 치료를 위한 도구로 광범위하게 사용될 수 있음이 입증되고 있으며, 이러한 이유로 엑소좀은 진단을 위한 바이오마커, 약물 전달을 위한 운반체 및 치료제로 활용될 수 있는가능성에 많은 연구자들의 관심이 높아지고 있다. 줄기세포 분야에서 엑소좀은 줄기세포를 기반으로 한 비세포 치료제로서 보다 안전한 치료제로 사용될 수 있다는 점에서 매력적인 소재가되고 있으며, 최근에는 중간엽줄기세포 유래 엑소좀이 항염증및 면역조절능이 있어 코로나-19 증상 완화 효능에 대한 안전성과 효능이 입증되기도 했다. 이렇게 계속적인 엑소좀에 대한 축적된 연구는 임상 진단 및 치료를 위한 차세대 혁신적 결과물들을 제공할 것으로 생각되며, 이 종설에서는 엑소좀의 다양한 가치에 초점을 두고 미래의학의 강력한 도구로 어떻게 활용될 수있는지에 대한 엑소좀의 잠재력을 살펴보고자 한다. Exosomes are nano-sized membrane-bound extracellular vesicles containing various biological molecules, such as nucleic acids, proteins, and lipids, which can be used to modulate physiological processes. The exosomal molecules secreted by cells can be extensively used as tools for diagnosis and therapy. Exosomes carry specific molecules released by the cells they originate from, which can be transferred to surrounding cells or tissues by the exosome. For these reasons, exosomes can be exploited as biomarkers for diagnosis, carriers for drug delivery, as well as therapeutics. In stem cell technology, exosomes have been an attractive option because they can be used as safer therapeutic agents for stem cell-based cell-free therapy. Recently, studies have demonstrated the safety and efficacy of mesenchymal stem cell-derived exosomes in alleviating symptoms associated with coronavirus disease 2019 as they have anti-inflammatory and immunomodulatory potential. Performing multiple studies on exosomes would provide innovative next-generation options for clinical diagnostics and therapy. This review summarizes the use of exosomes focusing on their diverse roles. In addition, the potential of exosomes is illustrated with a focus on how exosomes can be exploited as powerful tools in the days to come.

Poly-L-lysine Prevents Senescence and Augments Growth in Culturing Mesenchymal Stem Cells <i> Ex Vivo</i>

Heo, June Seok,Kim, Hyun Ok,Song, Seung Yong,Lew, Dae Hyun,Choi, Youjeong,Kim, Sinyoung Hindawi Publishing Corporation 2016 BioMed research international Vol.2016 No.-

<P>Mesenchymal stem cells (MSCs) possess great therapeutic potential. Efficient<I> in vitro</I> expansion of MSCs is however necessary for their clinical application. The extracellular matrix (ECM) provides structural and biochemical support to the surrounding cells, and it has been used as a coating substrate for cell culture. In this study, we have aimed to improve the functionality and stemness of MSCs during culture using poly-L-lysine (PLL). Functionality of MSCs was analysed by cell cycle analysis, differentiation assay, β-galactosidase staining, and RT-PCR. Furthermore, we assessed the global gene expression profile of MSCs on uncoated and PLL-coated plates. MSCs on PLL-coated plates exhibited a faster growth rate with increased S-phase and upregulated expression of the stemness markers. In addition, their osteogenic differentiation potential was increased, and genes involved in cell adhesion, FGF-2 signalling, cell cycle, stemness, cell differentiation, and cell proliferation were upregulated, compared to that of the MSCs cultured on uncoated plates. We also confirmed that MSCs on uncoated plates expressed higher β-galactosidase than the MSCs on PLL-coated plates. We demonstrate that PLL provides favourable microenvironment for MSC culture by reversing the replicative senescence. This method will significantly contribute to effective preparation of MSCs for cellular therapy.</P>

하악골 신장술에서 압축자극을 통한 골 재생방식에 대한 생체 역학적 평가

허준(June Heo),김욱규(Uk-Kyu Kim),황대석(Dae-Seok Hwang),김용덕(Yong-Deok Kim),신상훈(Sang-Hun Shin),정인교(In-Kyo Chung),김철훈(Cheol-Hun Kim),윤석영(Seok-Young Yun) 대한구강악안면외과학회 2007 대한구강악안면외과학회지 Vol.33 No.5

The purpose of this study was to investigate the clinical, biomechanical, and histologic changes in new distraction osteogenesis (DO) technique combined with a compression stimulation in accordance to different compression-distraction force ratio. 23 adult male rabbits underwent open-osteotomy at the mandibular body area and a external distraction device was applied. In the control group of 8 rabbits, only a 8 mm of distraction was performed by conventional DO technique. In an experimental group of 15 rabbits, a distraction followed by a compression force was performed according to the ratio of compression-distraction suggested by authors. The rate of experimental group I was set up as a 2 mm compression versus 10 mm distraction and the rate of experimental group II was set up as a 3 mm compression versus 11 mm distraction. All the rabbits were sacrificed for a gross finding, biomechanical, histomorphometric and histologic findings at the time of 55 days from the operation day. The results were as follows: 1. On the gross findings, because all rabbits had a sufficient healing time, every distracted new bone had good bone quality and we could not find any difference among all three groups. 2. In the histologic findings, rapid bone maturation (wide lamellar bone formation in the cancellous and cortical bone areas) was observed in two experimental groups compared to the control group. 3. On the bone density tests, the experimental group II showed higher bone density than the other experimental group and control group (control group - 0,2906 g/cm2, experimental group I - 0.2961 g/cm2, experimental group II - 0.3328 g/cm2). 4. On the biomechanical tests, the experimental group II had significantly higher bone microhardness than the other experimental group and control group (control group - 252.7 MPa, experimental group I - 263.5 MPa, experimental group II - 426.0 MPa). 5. On the microhardness tests, when we compared the hardness ratio of distracted bone versus normal bone, we could find experimental group II had significantly higher hardness ratio than the other experimental group and control group (control group - 0.47, experimental group I - 0.575, experimental group II - 0.80). From this study, we could deduce that the modified distraction osteogenesis method with a compression stimulation might improve the quality of bone regeneration and shorten the consolidation period in comparison with conventional distraction osteogenesis techniques

패턴된 폴리머를 이용한 중간엽줄기세포의 연골 분화

허준석 ( June Seok Heo ) 대한임상검사과학회 2015 대한임상검사과학회지(KJCLS) Vol.47 No.3

Mesenchymal stem cells (MSCs) are an attractive tool in tissue engineering as they have the required potential to treat injured articular cartilage. UV-exposed DTOPV (S-triazine bridged p-phenylene vinylene) is a biocompatible and fluorescent polymer with a hydrophilic surface. Previous studies have demonstrated that the surface wettability and hydrophilicity play critical roles in regulating cell adhesion and proliferation. The objective of this study was to improve the potential of in vitro MSC differentiation into Chondrocytes using DTOPV. MSCs were cultured on two different substrates: (1) tissue culture polystyrene (TCPS) as a reference and (2) UV-exposed and patterned DTOPV films. Chondrogenesis of MSCs was induced for two weeks on TCPS and DTOPV in the presence of an induction medium containing transforming growth factor (TGF)- 3. Interestingly, the MSCs on TCPS adhered and spread, while those on DTOPV tended to form aggregates within several days. The cells cultured on DTOPV for two weeks had a round morphology, with stronger Safranine O staining of the extracellular matrix than that of the cells cultured on TCPS. Also, Type II collagen gene was significantly expressed in cells induced on DTOPV. These results indicate that chondrogenic differentiation of MSCs proceeds more rapidly on DTOPV than on TCPS. Therefore, in cartilage tissue engineering, DTOPV could be used to induce effective chondrogenic differentiation of MSCs.

Clinical Value of Whole Body F-18 FDG PET in The Management of Recurrent Colorectal Malignancy

Seok-Byung Lim,Hyo Seong Choi,Sung-Bum Kang,Seung Chul Heo,Young Jin Park,Seung-Yong Jeong,Kyu Joo Park,Han-Kwang Yang,Kyung-Hoon Hwang,Jae-Min Jeong,Dong Soo Lee,June-Key Chung,Myung Chul Lee,Keon Wo 대한암학회 2003 Cancer Research and Treatment Vol.35 No.4

Design and Fabrication of a Disposable Nanoactuator Using 3D Printing

June Sik Hwang,Jin Seok Heo,Jong Eun Park,Jung-Ho Park,Euisu Lim,Sun Woo Kim,Hu-Seung Lee 한국정밀공학회 2021 International Journal of Precision Engineering and Vol.22 No.9

Nanoscale patterning has been widely used in various research fields. Conventional technology, however, has its limitations such as high cost and complicated processes. Recently, many alternative processes have been proposed to replace them. The major requirement for such an alternative process is that it does not require a mask, it must be capable of being processed at room temperature, and it needs to be an eco-friendly process. Photo electrophoretic deposition is a promising process that has various advantages, but it needs nanoscale movement of the reaction cell. In this study, a disposable nanoactuator was designed and manufactured to utilize the photo electrophoretic deposition process. In designing the nanoactuator, it is possible to accurately hold the position in the order of hundreds of nanometers for tens of seconds. The main variables are optimized to have a structure that can cause only single-axis displacement in a desired direction. Also, based on this design, the nanoactuator was fabricated by a 3D printer to verify its effectiveness. As a result, it was possible to manufacture an actuator that satisfies the desired performance, and a device will be fabricated by utilizing the actuator in a photo electrophoretic deposition process.

Nanoparticle emissions of partial premixed charge compression ignition (PPCCI) engines at diesel-gasoline dual fuel combustion

( June Pyo Cha ),( Seok Joo Kwon ),( Jeong Yoon Heo ),( Seung Hyun Yoon ),( Chang Sik Lee ),( Sung Wook Park ) 한국액체미립화학회 2010 한국액체미립화학회 학술강연회 논문집 Vol.2010 No.-

This paper describes combustion, emissions, and nanoparticles characteristics in partial premixed charge compression ignition (PPCCI) engines using diesel-gasoline dual fuel. Gasoline fuel was injected into premixed chamber installed in intake port in order to provide premixed mixture. On the other hand, diesel was injected directly into the combustion chamber to trigger combustion at 50MPa injection pressure using high pressure common-rail system. The present experiments were focused on advanced injection timings for diesel fuel (i.e., from 50 to 128oCA BTDC) in order to operate at partial premixed compression ignition (PPCCI) regimes. The total fueling quantity was kept at 10 mg/cyc. for three cases such as Gratio0% (diesel 10mg/cyc.), Gratio60% (diesel 4mg/cyc.+Gasoline 6mg/cyc.), and Gratio70% (diesel 3mg/cyc.+Gasoline 7mg/cyc.). In order to analyze effect of diesel-gasoline dual fuel on nanoparticles characteristics in PPCCI operation range, nanoparticle number and particle size distribution were measured by using a scanning mobility particle sizer (SMPS, Model 3936, TSI) and the measured mobility equivalent particle diameter range was from 10.6 nm to 385.4 nm. In was found that diesel-gasoline dual fuel combustion mode maintained stable combustion for advanced diesel injection cases for partial premixed charge compression ignition and increase in premixed gasoline fuel improved indicated mean effective pressure (IMEP). Furthermore, the total concentration of particle number of dual fuel combustion at PPCCI regime was increased significantly compared to those of conventional combustion near TDC.

Modified Damage Initiation Criterion for the Cohesive Boundary Element

Lee, Seok-Soon,Heo, Do-Eun,Lee, June-Key 한국정밀공학회 2010 International Journal of Precision Engineering and Vol.11 No.4

Cohesive models are increasingly applied to simulate fracture and fragmentation processes in various materials. The multiple-domain boundary element method (MDBEM) may be more suitable than the often-applied finite-element method (FEM) because debonding is also a boundary surface problem. In this study, a modified damage initiation criterion possessing a linear relationship to the MDBEM is proposed for the cohesive model. Numerical examples are presented to demonstrate the validity of this procedure.

COX-2 targeting indomethacin conjugated fluorescent probe

Kim, Hyeong Seok,Park, Taegun,Ren, Wen Xiu,Lim, Ja-Yun,Won, Miae,Heo, June Seok,Lee, Seung Gwan,Kim, Jong Seung Elsevier 2018 Dyes and pigments Vol.150 No.-

<P><B>Abstract</B></P> <P>The COX-2 targeting indomethacin-conjugated fluorescent probe <B>IQ-1</B> was synthesized newly for selective fluorescence imaging of cancer cells over normal cells. <B>IQ-1</B> caused stronger fluorescencc imaging of COX-2 overexpressing cancer cells (OVCAR3, HepG2 and Hela cells) than of normal cell lines (RAW 246.7 and fibroblast cells). LPS, an oxidative stress agent, treated inflamed cell lines inducing high COX-2 levels also revealed an enhanced fluorescence. In inhibitory studies, a markedly reducd fluorescence intensity was observed in cancer cells co-treated with an inhibitor, such as indomethacin and aceclofenac. Therefore, <B>IQ-1</B> can be used as a selective bioimaging agent for cancer cells over normal cells, and could be developed for efficient diagnosis and therapeutic monitoring in precision medicine.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The first chromenone fluorescent probe conjugated with indomethacin for COX-2 overexpressed cancer cells. </LI> <LI> Non-toxic under biological environments. </LI> <LI> Marked selectivity of probe <B>IQ-1</B> toward cancer cells over normal cells. </LI> <LI> Increased fluorescence of <B>IQ-1</B> in cell lines upon treatment of LPS (inducing oxidative stress) enhancing the COX-2 level. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>