Publications by authors named "Jaesung Park"

95 Publications

Urinary exosomal microRNA profiling in intermediate-risk prostate cancer.

Sci Rep 2021 Apr 1;11(1):7355. Epub 2021 Apr 1.

Catholic Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

MicroRNAs (miRNAs) of urine exosomes have emerged as biomarkers for urological cancers, owing to their high stability. MiRNAs have been linked to factors associated with aggressive prostate cancer such as biochemical recurrence (BCR) and metastasis. In this study, we aimed to identify urinary exosomal miRNAs as prognostic markers associated with BCR in intermediate-risk prostate cancer. We profiled the expression levels of miRNAs via next generation sequencing in urinary exosomes from 21 non-BCR patients and 6 BCR patients of intermediate-risk prostate cancer. A total of 21 urinary exosomal miRNAs were found to be differentially expressed (> twofold) in BCR patients compared to non-BCR patients. For external validation, we validated these results using quantitative reverse transcription PCR in an independent cohort of 28 non-BCR patients and 26 BCR patients. A validation analysis revealed that three miRNAs (miR-26a-5p, miR-532-5p, and miR-99b-3p) were upregulated in exosomes from BCR patients. The univariate and multivariate Cox regression analyses showed that miR-532-5p was an important predictive factor for BCR of intermediate-risk prostate cancer. In conclusion, miR-532-5p in urine exosomes might be a potential biomarker for predicting BCR, which is a poor prognosis in patients with intermediate-risk prostate cancer. Further research is needed on the biological functions and mechanisms of this miRNA.
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http://dx.doi.org/10.1038/s41598-021-86785-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016942PMC
April 2021

Machine Learning-Based Microclimate Model for Indoor Air Temperature and Relative Humidity Prediction in a Swine Building.

Animals (Basel) 2021 Jan 18;11(1). Epub 2021 Jan 18.

Department of Bio-Systems Engineering, Institute of Smart Farm, Gyeongsang National University, Jinju 52828, Korea.

Indoor air temperature (IAT) and indoor relative humidity (IRH) are the prominent microclimatic variables; still, potential contributors that influence the homeostasis of livestock animals reared in closed barns. Further, predicting IAT and IRH encourages farmers to think ahead actively and to prepare the optimum solutions. Therefore, the primary objective of the current literature is to build and investigate extensive performance analysis between popular ML models in practice used for IAT and IRH predictions. Meanwhile, multiple linear regression (MLR), multilayered perceptron (MLP), random forest regression (RFR), decision tree regression (DTR), and support vector regression (SVR) models were utilized for the prediction. This study used accessible factors such as external environmental data to simulate the models. In addition, three different input datasets named S1, S2, and S3 were used to assess the models. From the results, RFR models performed better results in both IAT (R = 0.9913; RMSE = 0.476; MAE = 0.3535) and IRH (R = 0.9594; RMSE = 2.429; MAE = 1.47) prediction among other models particularly with S3 input datasets. In addition, it has been proven that selecting the right features from the given input data builds supportive conditions under which the expected results are available. Overall, the current study demonstrates a better model among other models to predict IAT and IRH of a naturally ventilated swine building containing animals with fewer input attributes.
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http://dx.doi.org/10.3390/ani11010222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831115PMC
January 2021

Single-vesicle imaging and co-localization analysis for tetraspanin profiling of individual extracellular vesicles.

J Extracell Vesicles 2021 Jan 11;10(3):e12047. Epub 2021 Jan 11.

Department of Mechanical Engineering Pohang University of Science and Technology Pohang Gyeong-buk Republic of Korea.

Extracellular vesicles (EVs) are secreted nano-sized vesicles that contain cellular proteins, lipids, and nucleic acids. Although EVs are expected to be biologically diverse, current analyses cannot adequately characterize this diversity because most are ensemble methods that inevitably average out information from diverse EVs. Here we describe a single vesicle analysis, which directly visualizes marker expressions of individual EVs using a total internal-reflection microscopy and analyzes their co-localization to investigate EV subpopulations. The single-vesicle imaging and co-localization analysis successfully illustrated the diversity of EVs and revealed distinct patterns of tetraspanin expressions. Application of the analysis demonstrated similarities and dissimilarities between the EV fractions that had been acquired from different conventional EV isolation methods. The analysis method developed in this study will provide a new and reliable tool for investigating characteristics of single EVs, and the findings of the analysis might increase understanding of the characteristics of EVs.
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http://dx.doi.org/10.1002/jev2.12047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797949PMC
January 2021

Heterogeneous Subcellular Origin of Exosome-Mimetic Nanovesicles Engineered from Cells.

ACS Biomater Sci Eng 2020 11 29;6(11):6063-6068. Epub 2020 Oct 29.

Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Gyeong-buk 37673, Republic of Korea.

Cell-engineered nanovesicles (CNVs) are considered as an alternative to exosomes, because they can be produced efficiently on a large scale and have been successfully reported in several applied research studies. However, CNVs may originate from various organelles, i.e., some of them may cause adverse effects on recipient cells, and their origin has not yet been identified. In this study, we air-sprayed human embryonic kidney 293 (HEK293) cells into lipid-bilayer CNVs. To identify the subcellular origin of the CNVs, we prepared nine different HEK293 cell lines by transfection with organelle-specific fluorescent protein plasmids that target the plasma membrane, peroxisome, lysosome, early endosome, late endosome, nucleus, mitochondrion, Golgi apparatus, and endoplasmic reticulum. The origin of CNVs were identified by measuring fluorescence expressions for organelle-specific markers using fluorescence nanoparticle tracking analysis (NTA). In the results, we found that CNVs derived from the plasma membrane constituted the largest portion, but CNVs derived from the other organelles comprised a non-negligible portion as well. This information will be useful to guide advanced research on outer membrane vesicles and exosome-mimetic nanovesicles engineered from cells.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01157DOI Listing
November 2020

Surgical Outcomes and Predictive Factors of Medial Toe Excision for Polysyndactyly of the Fifth Toe.

Foot Ankle Int 2020 Nov 16:1071100720971289. Epub 2020 Nov 16.

Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: We aimed to report surgical outcomes and analyze prognostic factors of medial toe excision for polysyndactyly of the fifth toe.

Methods: We reviewed the details of 139 consecutive patients who underwent surgery for postaxial polydactyly of the foot from 2009 to 2018. Among these, 83 patients (90 feet) with polysyndactyly of the fifth toe, treated by medial toe excision (between the duplicated toes) and reconstruction of the fourth web space using a dorsal rectangular flap, were included. The toe alignment and stability were restored by chondroplasty and soft tissue balancing without an osteotomy. A full-thickness skin graft was performed in 52 feet. The mean age at surgery was 27.1 ± 17.5 months and the mean duration of follow-up was 42.8 ± 24.9 months.

Results: At the last follow-up, a relatively small size of the reconstructed toe was observed in 19 feet (19/90, 21.1%). Proximal duplication level (metatarsal or proximal phalanx type) and preoperative hypoplasia of the remaining toe were related to the small postoperative size. Valgus deformity of the remaining toe was observed in 2 feet (2/90, 2.2%). We observed 17 cases with delayed healing or early postoperative wound infection. Among these, 7 cases (7/90, 7.8%) showed postoperative thickening or advancement of the web, which was not observed in cases without wound problems. No cases had functional disturbance or pain.

Conclusion: The overall surgical outcomes were satisfactory without an osteotomy. Patients with a proximal duplication level or preoperative hypoplasia of the remaining toe should be informed of its possible small size postoperatively.

Levels Of Evidence: Level IV, retrospective case series.
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http://dx.doi.org/10.1177/1071100720971289DOI Listing
November 2020

Tailoring molecular interactions between microporous polymers in high performance mixed matrix membranes for gas separations.

Nanoscale 2020 Aug;12(33):17405-17410

CSIRO, Bag 10, Clayton South, VIC 3169, Australia. and Department of Chemical Engineering, Monash University, Clayton, VIC 3169, Australia.

Membranes are crucial to lowering the huge energy costs of chemical separations. Whilst some promising polymers demonstrate excellent transport properties, problems of plasticisation and physical aging due to mobile polymer chains, amongst others, prevent their exploitation in membranes for industrial separations. Here we reveal that molecular interactions between a polymer of intrinsic microporosity (PIM) matrix and a porous aromatic framework additive (PAF-1) can simultaneously address plasticisation and physical aging whilst also increasing gas transport selectivity. Extensive spectroscopic characterisation and control experiments involving two near-identical PIMs, one with methyl groups (PIM-EA(Me2)-TB) and one without (PIM-EA(H2)-TB), directly confirm the key molecular interaction as the adsoprtion of methyl groups from the PIM matrix into the nanopores of the PAF. This interaction reduced physical aging by 50%, suppressed polymer chain mobilities at high pressure and increased H2 selectivity over larger gases such as CH4 and N2.
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http://dx.doi.org/10.1039/d0nr04801aDOI Listing
August 2020

Development of Willow Tree Yield-Mapping Technology.

Sensors (Basel) 2020 May 6;20(9). Epub 2020 May 6.

Ramea Phytotechnologies, Saint-Roch-de-l'Achigan, QC, J0K 3H0, Canada.

With today's environmental challenges, developing sustainable energy sources is crucial. From this perspective, woody biomass has been, and continues to be, a significant research interest. The goal of this research was to develop new technology for mapping willow tree yield grown in a short-rotation forestry (SRF) system. The system gathered the physical characteristics of willow trees on-the-go, while the trees were being harvested. Features assessed include the number of trees harvested and their diameter. To complete this task, a machine-vision system featuring an RGB-D stereovision camera was built. The system tagged these data with the corresponding geographical coordinates using a Global Navigation Satellite System (GNSS) receiver. The proposed yield-mapping system showed promising detection results considering the complex background and variable light conditions encountered in the outdoors. Of the 40 randomly selected and manually observed trees in a row, 36 were successfully detected, yielding a 90% detection rate. The correctly detected tree rate of all trees within the scenes was actually 71.8% since the system tended to be sensitive to branches, thus, falsely detecting them as trees. Manual validation of the diameter estimation function showed a poor coefficient of determination and a root mean square error (RMSE) of 10.7 mm.
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http://dx.doi.org/10.3390/s20092650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249128PMC
May 2020

Lotus seedpod-inspired hydrogels as an all-in-one platform for culture and delivery of stem cell spheroids.

Biomaterials 2019 12 30;225:119534. Epub 2019 Sep 30.

Department of Bioengineering, Hanyang University, 222 Wangsimri-ro, Seongdong-gu, Seoul, 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, 222 Wangsimri-ro, Seongdong-gu, Seoul, 04763, Republic of Korea. Electronic address:

3D culture of stem cells can improve therapeutic effects. However, there is limited research on how to deliver cultured stem cell spheroids to the desired target. Here, we developed lotus seedpod-inspired hydrogel (LoSH) containing microwells for culture and delivery of stem cell spheroids. Human adipose-derived stem cells (hADSCs) inside the square microwells (200 or 400 μm in width with various depths) spontaneously formed spheroids with high viability (94.08 ± 1.56%), and fibronectins conjugated to the hydrogel successfully gripped the spheroids, similar to the funiculus gripping seeds in the lotus seedpod. The spheroids slightly bound to the LoSH surface at 37 °C were detached by the expansion of LoSH at lower temperature of 4 °C. After spheroid formation, LoSH was placed on the target substrate upside-down, expanded at 4 °C for 10 min, and removed from the target. As a result, the spheroids within the microwell were successfully transferred to the target substrate with high transfer efficiency (93.78 ± 2.30%). A delivery of spheroids from LoSH to full-thickness murine skin wound with chimney model showed significant enhancement of the number of SMA-positive vessels at day 21 compared to the group received the same number of spheroids by injection. Together, our findings demonstrate LoSH as a one-step platform that can culture and deliver spheroids to a large target area, which will be useful for various biomedical applications.
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http://dx.doi.org/10.1016/j.biomaterials.2019.119534DOI Listing
December 2019

Fabrication of core-shell spheroids as building blocks for engineering 3D complex vascularized tissue.

Acta Biomater 2019 12 19;100:158-172. Epub 2019 Sep 19.

Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University. Electronic address:

Cell spheroids as building blocks for engineering micro-tissue should be able to mimic the complex structure of natural tissue. However, control of the distribution of multiple cell populations within cell spheroids is difficult to achieve with current spheroid-harvest methods such as hanging-drop and with the use of microwell plates. In this study, we report the fabrication of core-shell spheroids with the ultimate goal to form 3D complex micro-tissue. We used endothelial cells and two types of stem cells (human turbinate mesenchymal stem cells (hTMSCs)/adipose-derived stem cells (ADSCs)). The stem cells and endothelial cells formed layered micro-sized cell sheets (µCSs) on polydopamine micro-patterned temperature-responsive hydrogel surfaces by a sequential seeding method, and these layered µCSs self-assembled to form core-shell spheroids by expansion of the hydrogels. The co-cultured spheroids formed a core-shell structure irrespective of stem cell type. In addition, the size of the core-shell spheroids was controlled from 90 ± 1 to 144 ± 3 µm by changing pattern sizes (200, 300, and 400 µm). The shell thickness gradually increased from 12 ± 3 to 30 ± 6 µm by adjusting the endothelial cell seeding density. Finally, we fabricated the micro-tissue by fusion of the co-cultured spheroids, and the spheroids with the core-shell structure rapidly induced in vitro vessel-like network in 3 days. Thus, the position of endothelial cells in co-cultured spheroids may be an important factor for the modulation of the vascularization process, which can be useful for the production of 3D complex micro-tissues using spheroids as building blocks. STATEMENT OF SIGNIFICANCE: This manuscript describes our work on the fabrication of core-shell spheroids as building blocks to form 3D complex vascularized micro-tissue. Stem cells (human turbinate mesenchymal stem cells (hTMSCs) or adipose-derived stem cells (ADSCs)) and endothelial cells formed layered micro-sized cell sheets (µCSs) on micro-patterned temperature-responsive hydrogel surfaces by a sequential seeding method, and these layered µCSs self-assembled to form core-shell spheroids (core - stem cells, shell - endothelial cells), irrespective of stem cell type. In addition, the size and shell thickness of the core-shell spheroids were controlled by modifying pattern size and endothelial cell seeding density. We fabricated the vascularized micro-tissue by fusion of the spheroids and demonstrated that the spheroids with a core-shell structure rapidly induced vessel-like network.
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http://dx.doi.org/10.1016/j.actbio.2019.09.028DOI Listing
December 2019

Size-based analysis of extracellular vesicles using sequential transfer of an evaporating droplet.

Lab Chip 2019 10 9;19(19):3326-3336. Epub 2019 Sep 9.

Mechanical Engineering, POSTECH, Republic of Korea. and School of Interdisciplinary Bioscience and Bioengineering, POSTECH, Republic of Korea and Center for Wireless Integrated MicroSensing and Systems, University of Michigan, Ann Arbor, USA.

We report spatial separation of extracellular vesicle (EVs) populations based on particle size by using an approach that exploits Marangoni flow and the coffee-ring effect in microdroplets. Sequential transfer of a drying droplet progressively increases the mean size of EVs in the sample by repeated subsampling of a droplet during coffee-ring formation. This method allows size-based sorting, separation, and eventual retrieval of EVs for RNA and protein analysis. To demonstrate the biomedical relevance of this method, EVs from prostate cancer patients were analyzed; results revealed that the expression of cancer-associated genes and proteins was higher in small EVs than in large EVs. This ability to sort EVs using a combination of coffee ring with Marangoni flow and sequential droplet-transfer allows analysis of subpopulations of EVs, and will facilitate further studies of EVs.
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http://dx.doi.org/10.1039/c9lc00526aDOI Listing
October 2019

Fabrication of cell membrane-adhesive soft polymeric nanovehicles for noninvasive visualization of epidermal-dermal junction-targeted drug delivery.

Int J Pharm 2019 Jun 7;565:233-241. Epub 2019 May 7.

Department of Bionano Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 15588, Republic of Korea; Department of Chemical and Molecular Engineering, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 15588, Republic of Korea. Electronic address:

We propose a polymeric nanovehicles (PNVs)-based enhanced transdermal delivery platform. A technical advance can be found in that delivery efficiency is significantly enhanced by effective adhesion of PNVs to the cell membrane, which is characterized noninvasively by using a confocal laser scanning microscopy (CLSM)-based skin visualization technique. To this end, the PNVs with a soft core phase were fabricated through co-assembly of two amphiphilic triblock copolymers, poly(ethylene oxide)-b-poly(ε-caprolactone)-b-poly(ethylene oxide) (PEO-b-PCL-b-PEO) and poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-b-PPO-b-PEO). The softness of PNVs was tuned successfully, while maintaining the particle size at ∼110 nm, by incorporation of PEO-b-PPO-b-PEO into the PNVs to a volume fraction of 0.3. Through an ex vivo skin penetration test, we showed that transactivating transcriptional activator (TAT)-decorated soft PNVs could not only exert strong adhesion to skin but also increase cellular uptake, leading to a transdermal delivery efficiency that is twice that of a hard PNV control. Moreover, CLSM-based noninvasive visualization of a fluorescent drug probe in the skin showed that the adhesiveness and softness of the PNVs contributed directly to the enhancement of transdermal delivery.
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http://dx.doi.org/10.1016/j.ijpharm.2019.05.014DOI Listing
June 2019

Author Correction: Prostate-specific extracellular vesicles as a novel biomarker in human prostate cancer.

Sci Rep 2019 Apr 15;9(1):6051. Epub 2019 Apr 15.

Department of Urology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has not been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-019-41385-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465358PMC
April 2019

Microstructural engineering in interface-type synapse device for enhancing linear and symmetric conductance changes.

Nanotechnology 2019 Jul 10;30(30):305202. Epub 2019 Apr 10.

Department of Materials Science and Engineering, Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea.

The origins of the nonlinear and asymmetric synaptic characteristics of TiO -based synapse devices were investigated. Based on the origins, a microstructural electrode was utilized to improve the synaptic characteristics. Under an identical pulse bias, a TiO -based synapse device exhibited saturated conductance changes, which led to nonlinear and asymmetric synaptic characteristics. The formation of an interfacial layer between the electrode and TiO layer, which can limit consecutive oxygen migration and chemical reactions, was considered as the main origin of the conductance saturation behavior. To achieve consecutive oxygen migration and chemical reactions, structural engineering was utilized. The resultant microstructural electrode noticeably improved the synaptic characteristics, including the unsaturated, linear, and symmetric conductance changes. These synaptic characteristics resulted in the recognition accuracy significantly increasing from 38% to 90% in a neural network-based pattern recognition simulation.
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http://dx.doi.org/10.1088/1361-6528/ab180fDOI Listing
July 2019

Mesenchymal Stem Cell Engineered Nanovesicles for Accelerated Skin Wound Closure.

ACS Biomater Sci Eng 2019 Mar 15;5(3):1534-1543. Epub 2019 Feb 15.

Department of Mechanical Engineering, POSTECH, 77 Cheongam-Ro, Nam-Gu, Pohang, Gyeongbuk 37673, Republic of Korea.

We report development and characterization of cell-engineered nanovesicles made from mesenchymal stem cells (MSCNVs), which have more than 300 times higher productivity than natural extracellular vesicles (EVs). MSCNVs had similar morphological characteristics to MSCEVs but have molecular characteristics that more resemble MSCs than MSCEVs. MSCNV treatment increased the proliferation and migration of primary skin fibroblasts and showed better effects than treatment using natural MSCEVs. Quantitative real-time PCR analysis showed increased expression of growth factors in MSCNV-treated skin fibroblasts. Intraperitoneal injection of MSCNVs into syngeneic mice induced mild local inflammation, which resulted in recruitment of immune cells to the injection site. MSCNV treatment of a mouse skin wound accelerated its healing; this acceleration by MSCNVs may occur by promoting blood vessel formation at the wound site. These results indicate the promise of MSCNVs as agents for regenerative medicine.
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http://dx.doi.org/10.1021/acsbiomaterials.8b01646DOI Listing
March 2019

Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines.

J Extracell Vesicles 2018 23;7(1):1535750. Epub 2018 Nov 23.

Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council (CNR) of Italy, Palermo, Italy.

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
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http://dx.doi.org/10.1080/20013078.2018.1535750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322352PMC
November 2018

Hydrogels with an embossed surface: An all-in-one platform for mass production and culture of human adipose-derived stem cell spheroids.

Biomaterials 2019 01 22;188:198-212. Epub 2018 Oct 22.

Department of Bioengineering, Hanyang University, 222 Wangsimri-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, 222 Wangsimri-ro, Seongdong-gu, Seoul 04763, Republic of Korea; Institute of Nano Science & Technology (INST), Hanyang University, 222 Wangsimri-ro, Seongdong-gu, Seoul 04763, Republic of Korea. Electronic address:

Stem cell spheroids have been studied extensively in organoid culture and therapeutic transplantation. Herein, hydrogels with an embossed surface (HES) were developed as an all-in-one platform that can enable the rapid formation and culture of a large quantity of size-controllable stem cell spheroids. The embossed structure on the hydrogel was adjustable according to the grit designation of the sandpaper. Human adipose-derived stem cells (hADSCs) were rapidly assembled into spheroids on the hydrogel, with their size distribution precisely controlled from 95 ± 6 μm to 181 ± 15 μm depending on surface roughness. The hADSC spheroids prepared from the HES demonstrated expression of stemness markers and differentiation capacity. In addition, HES-based spheroids showed significantly greater VEGF secretion than spheroids grown on a commercially available low-attachment culture plate. Exploiting those advantages, the HES-based spheroids were used for 3D bioprinting, and the spheroids within the 3D-printed construct showed improved retention and VEGF secretion compared to the same 3D structure containing single cell suspension. Collectively, HES would offer a useful platform for mass fabrication and culture of stem cell spheroids with controlled sizes for a variety of biomedical applications.
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http://dx.doi.org/10.1016/j.biomaterials.2018.10.025DOI Listing
January 2019

Sepsis-Like Systemic Inflammation Induced by Nano-Sized Extracellular Vesicles From Feces.

Front Microbiol 2018 7;9:1735. Epub 2018 Aug 7.

Department of Life Sciences, Pohang University of Science and Technology, Pohang, South Korea.

Nano-sized extracellular vesicles (EVs), including exosomes, microvesicles, and other types of vesicles, are released by most mammalian cells and bacteria. We here ask whether feces contain EVs of mammalian and/or bacterial origin, and whether these EVs induce systemic inflammation. Fecal extracellular vesicles (fEVs) were isolated from mice and humans. The presence of EVs from Gram-negative and Gram-positive bacteria was detected by enzyme-linked immunosorbent assay using anti-lipid A and anti-lipoteichoic acid antibodies, whereas Western blot using anti-beta-actin antibody was employed to detect host-derived EVs in the fEVs. Further, fEVs were administered into mice by intraperitoneal injection, and inflammatory responses were investigated in the peritoneum, blood, and lungs. The role of TLR2 and TLR4 were studied using knockout mice. Significant quantities of EVs were present in feces from mice as well as humans, and derived from Gram-negative and Gram-positive bacteria, as well as the host. Bacteria-free fEVs introduced into the peritoneum induced local and systemic inflammation (including in the lungs), but fEVs from germ-free animals had weaker effects. This pronounced local and systemic inflammatory responses seemed to be induced by EVs from both Gram-negative and Gram-positive bacteria, and was attenuated in mice lacking TLR2 or TLR4. Our findings show that fEVs cause sepsis-like systemic inflammation, when introduced intraperitoneally, a process regulated by TLR2 and TLR4.
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http://dx.doi.org/10.3389/fmicb.2018.01735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090151PMC
August 2018

Cancer-derived exosomes trigger endothelial to mesenchymal transition followed by the induction of cancer-associated fibroblasts.

Acta Biomater 2018 08 4;76:146-153. Epub 2018 Jul 4.

Center for BioMicrosystems, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology (UST), Seoul 02792, Republic of Korea. Electronic address:

Cancer-associated fibroblasts (CAFs) play a pivotal role in tumor growth, but very little has been known about its characteristics and origin. Recently, cancer-derived exosome has been suggested to transdifferentiate CAFs, by a new mechanism of endothelial to mesenchymal transition (EndMT), initiating angiogenic processes and triggering metastatic evolution. However, an enabling tool in vitro is yet to be developed to investigate complicated procedures of the EndMT and the transdifferentiation under reconstituted tumor microenvironment. Here we proposed an in vitro microfluidic model which enables to monitor a synergetic effect of complex tumor microenvironment in situ, including extracellular matrix (ECM), interstitial flow and environmental exosomes. The number of CAFs differentiated from human umbilical vein endothelial cells (HUVECs) increased with melanoma-derived exosomes, presenting apparent morphological and molecular changes with pronounced motility. Mesenchymal stem cell (MSC)-derived exosomes were found to suppress EndMT, induce angiogenesis and maintain vascular homeostasis, while cancer-derived exosomes promoted EndMT. Capabilities of the new microfluidic model exist in precise regulation of the complex tumor microenvironment and therefore successful reconstitution of 3D microvasculature niches, enabling in situ investigation of EndMT procedure between various cell types.

Statement Of Significance: This study presents an in vitro 3D EndMT model to understand the progress of the CAF generation by recapitulating the 3D tumor microenvironment in a microfluidic device. Both cancer-derived exosomes and interstitial fluid flow synergetically played a pivotal role in the EndMT and consequent formation of CAFs through a collagen-based ECM. Our approach also enabled the demonstration of a homeostatic capability of MSC-derived exosomes, ultimately leading to the recovery of CAFs back to endothelial cells. The in vitro 3D EndMT model can serve as a powerful tool to validate exosomal components that could be further developed to anti-cancer drugs.
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http://dx.doi.org/10.1016/j.actbio.2018.07.001DOI Listing
August 2018

Analysis of Extracellular Vesicles Using Coffee Ring.

ACS Appl Mater Interfaces 2018 Jul 26;10(27):22877-22882. Epub 2018 Jun 26.

Center for Wireless Integrated MicroSensing and Systems , University of Michigan , Ann Arbor , Michigan 48109 , United States.

Extracellular vesicles are categorized in subsets according to their biogenesis processes. To facilitate the investigation of subsets, an effective method is needed for isolating subpopulations. The efficacy of existing density and size-based isolation methods is limited, and as a result, the correlation of properties within separated subpopulations is modest. Here, we introduced size separation with ∼48 nm resolution that exploits Marangoni flow and the coffee-ring effect in microdroplets in which extracellular vesicles are spatially deposited at different location according to size of extracellular vesicle. Interestingly, the analysis of tetraspanin proteins of the extracellular vesicles facilitated by this method reveals that the size of extracellular vesicles is correlated with expression of tetraspanin proteins (CD9, CD63, CD81) that are associated with the size of extracellular vesicles. The findings show that CD9 and CD81 are uniformly expressed regardless of size, CD63 is highly expressed only in larger extracellular vesicles. This evidence indicates that extracellular vesicles can be classified based on size and expression of CD63.
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http://dx.doi.org/10.1021/acsami.8b05793DOI Listing
July 2018

Aqueous two-phase system to isolate extracellular vesicles from urine for prostate cancer diagnosis.

PLoS One 2018 27;13(3):e0194818. Epub 2018 Mar 27.

Department of Mechanical Engineering, POSTECH, Pohang, Republic of Korea.

Analyzing extracellular vesicles (EVs) is an attractive approach to diagnosis of prostate diagnosis. However, existing methods of EVs isolation have low efficiency, purity, and long process time, and therefore have low diagnostic ability. To solve these the problems, a two-phase system is adapted to isolate EVs from a patient's urine. Urine from 20 prostate cancer (PCA) patients and 10 benign prostate hyperplasia patients was used to quantify the EVs-isolation ability of an aqueous two-phase system (ATPS) and to compare the diagnostic ability of ATPS with that of the conventional diagnosis method. An optimized ATPS isolates EVs with ~100% efficiency within ~30 min, with 14 times as high as achieved by ultracentrifugation. Afterward, PCR and ELISA are used to detect EVs derived from PCA cells in urine. The results demonstrate that diagnostic ability based on ATPS is better than other conventional diagnostic methods. ATPS can obtain a high quality and quantity of EVs from patients' urine. EVs contain cancer-related protein and genes, so these abundant sources enable diagnosis with high specificity and sensitivity. Therefore, ATPS is a useful tool to increase the specificity and sensitivity of diagnosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0194818PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870972PMC
July 2018

Large-scale polymeric carbon nanotube membranes with sub-1.27-nm pores.

Sci Adv 2018 03 9;4(3):e1700938. Epub 2018 Mar 9.

University of Texas, Austin, TX 78712, USA.

We report the first characterization study of commercial prototype carbon nanotube (CNT) membranes consisting of sub-1.27-nm-diameter CNTs traversing a large-area nonporous polysulfone film. The membranes show rejection of NaCl and MgSO at higher ionic strengths than have previously been reported in CNT membranes, and specific size selectivity for analytes with diameters below 1.24 nm. The CNTs used in the membranes were arc discharge nanotubes with inner diameters of 0.67 to 1.27 nm. Water flow through the membranes was 1000 times higher than predicted by Hagen-Poiseuille flow, in agreement with previous CNT membrane studies. Ideal gas selectivity was found to deviate significantly from that predicted by both viscous and Knudsen flow, suggesting that surface diffusion effects may begin to dominate gas selectivity at this size scale.
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http://dx.doi.org/10.1126/sciadv.1700938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844709PMC
March 2018

Strain-shear coupling in bilayer MoS.

Nat Commun 2017 11 8;8(1):1370. Epub 2017 Nov 8.

Department of Physics, Sogang University, Seoul, 04107, Korea.

Layered materials such as graphite and transition metal dichalcogenides have extremely anisotropic mechanical properties owing to orders of magnitude difference between in-plane and out-of-plane interatomic interaction strengths. Although effects of mechanical perturbations on either intralayer or interlayer interactions have been extensively investigated, mutual correlations between them have rarely been addressed. Here, we show that layered materials have an inevitable coupling between in-plane uniaxial strain and interlayer shear. Because of this, the uniaxial in-plane strain induces an anomalous splitting of the degenerate interlayer shear phonon modes such that the split shear mode along the tensile strain is not softened but hardened contrary to the case of intralayer phonon modes. We confirm the effect by measuring Raman shifts of shear modes of bilayer MoS under strain. Moreover, by analyzing the splitting, we obtain an unexplored off-diagonal elastic constant, demonstrating that Raman spectroscopy can determine almost all mechanical constants of layered materials.
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http://dx.doi.org/10.1038/s41467-017-01487-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678169PMC
November 2017

Gas molecule sensing of van der Waals tunnel field effect transistors.

Nanoscale 2017 Dec;9(47):18644-18650

Emerging Devices Research Group, Electronics and Telecommunications Research Institute (ETRI), 218 Gajeong-ro, Yuseong-gu, Daejeon, 34129, Korea.

van der Waals (vdW) heterostructures with two-dimensional (2D) crystals such as graphene, hexagonal boron nitride (hBN) and transition metal dichalcogenides (TMDCs) allow us to demonstrate atomically thin field-effect transistors (FETs), photodetectors (PDs) and photovoltaic devices capable of higher performance and greater stability levels than conventional devices. Although there have been studies of gas molecule sensing with 2D crystal channels, vdW heterostructures based on 2D crystals have not been employed thus far. Here, utilizing graphene/WS/graphene (G/WS/G) vdW heterostructure tunnel FETs, we demonstrate the rectification behavior of the sensitivity signal by tuning the WS potential barriers as a function of the gas molecule concentration and devise a fingerprint map of the sensitivity variation corresponding to an individual ratio of two different molecules in a gas mixture. Because the separation of different gas molecule concentrations from gas mixtures is in high demand in the gas-sensing research field, this result will greatly assist in the progress on selective gas sensing.
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http://dx.doi.org/10.1039/c7nr05712aDOI Listing
December 2017

Asymmetric Electron-Hole Decoherence in Ion-Gated Epitaxial Graphene.

Sci Rep 2017 09 21;7(1):12130. Epub 2017 Sep 21.

Center for Electricity and Magnetism, Korea Research Institute of Standards and Science, Daejeon, 34113, Republic of Korea.

We report on asymmetric electron-hole decoherence in epitaxial graphene gated by an ionic liquid. The observed negative magnetoresistance near zero magnetic field for different gate voltages, analyzed in the framework of weak localization, gives rise to distinct electron-hole decoherence. The hole decoherence rate increases prominently with decreasing negative gate voltage while the electron decoherence rate does not exhibit any substantial gate dependence. Quantitatively, the hole decoherence rate is as large as the electron decoherence rate by a factor of two. We discuss possible microscopic origins including spin-exchange scattering consistent with our experimental observations.
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http://dx.doi.org/10.1038/s41598-017-12425-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5608950PMC
September 2017

Anomalous Ambipolar Transport of Organic Semiconducting Crystals via Control of Molecular Packing Structures.

ACS Appl Mater Interfaces 2017 Aug 9;9(33):27839-27846. Epub 2017 Aug 9.

Department of Chemical Engineering, Pohang University of Science and Technology , Pohang 790-784, Korea.

Organic crystals deposited on 2-dimensional (2D) van der Waals substrates have been widely investigated due to their unprecedented crystal structures and electrical properties. van der Waals interaction between organic molecules and the substrate induces epitaxial growth of high quality organic crystals and their anomalous crystal morphologies. Here, we report on unique ambipolar charge transport of a "lying-down" pentacene crystal grown on a 2D hexagonal boron nitride van der Waals substrate. From in-depth analysis on crystal growth behavior and ultraviolet photoemission spectroscopy measurement, it is revealed that the pentacene crystal at the initial growth stage have a lattice-strained packing structure and unique energy band structure with a deep highest occupied molecular orbital level compared to conventional "standing-up" crystals. The lattice-strained pentacene few layers enable ambipolar charge transport in field-effect transistors with balanced hole and electron field-effect mobilities. Complementary logic circuits composed of the two identical transistors show clear inverting functionality with a high gain up to 15. The interesting crystal morphology of organic crystals on van der Waals substrates is expected to attract broad attentions on organic/2D interfaces for their electronic applications.
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http://dx.doi.org/10.1021/acsami.7b05129DOI Listing
August 2017

Cell-Engineered Nanovesicle as a Surrogate Inducer of Contact-Dependent Stimuli.

Adv Healthc Mater 2017 Sep 23;6(17). Epub 2017 Jun 23.

School of Interdisciplinary Bioscience and Bioengineering, POSTECH, 77 Cheongam-Ro Nam-gu, Engineering Building 5, Pohang, Gyeong-buk, 37673, Republic of Korea.

Heterotypic interactions between cells are crucial in various biological phenomena. Particularly, stimuli that regulate embryonic stem cell (ESC) fate are often provided from neighboring cells. However, except for feeder cultures, no practical methods are identified that can provide ESCs with contact-dependent cell stimuli. To induce contact-dependent cell stimuli in the absence of living cells, a novel method that utilizes cell-engineered nanovesicles (CNVs) that are made by extruding living cells through microporous membranes is described. Protein compositions of CNVs are similar to their originating cells, as well as freely diffusible and precisely scalable. Treatment of CNVs produced from three different stromal cells successfully induces the same effect as feeder cultures. The results suggest that the effects of CNVs are mainly mediated by membrane-associated components. The use of CNVs might constitute a novel and efficient tool for ESC research.
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http://dx.doi.org/10.1002/adhm.201700381DOI Listing
September 2017

Direct Probing of the Electronic Structures of Single-Layer and Bilayer Graphene with a Hexagonal Boron Nitride Tunneling Barrier.

Nano Lett 2017 01 27;17(1):206-213. Epub 2016 Dec 27.

Center for Theoretical Physics of Complex Systems, Institute for Basic Science , Daejeon 34051, Korea.

The chemical and mechanical stability of hexagonal boron nitride (h-BN) thin films and their compatibility with other free-standing two-dimensional (2D) crystals to form van der Waals heterostructures make the h-BN-2D tunnel junction an intriguing experimental platform not only for the engineering of specific device functionalities but also for the promotion of quantum measurement capabilities. Here, we exploit the h-BN-graphene tunnel junction to directly probe the electronic structures of single-layer and bilayer graphene in the presence and the absence of external magnetic fields with unprecedented high signal-to-noise ratios. At a zero magnetic field, we identify the tunneling spectra related to the charge neutrality point and the opening of the electric-field-induced bilayer energy gap. In the quantum Hall regime, the quantization of 2D electron gas into Landau levels (LL) is seen as early as 0.2 T, and as many as 30 well-separated LL tunneling conductance oscillations are observed for both electron- and hole-doped regions. Our device simulations successfully reproduce the experimental observations. Additionally, we extract the relative permittivity of three-to-five layer h-BN and find that the screening capability of thin h-BN films is as much as 60% weaker than bulk h-BN.
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http://dx.doi.org/10.1021/acs.nanolett.6b03821DOI Listing
January 2017

Nanoscale Direct Mapping of Noise Source Activities on Graphene Domains.

ACS Nano 2016 11 11;10(11):10135-10142. Epub 2016 Nov 11.

Center for Electricity & Magnetism, Korea Research Institute of Standards and Science , Daejeon 305-340, Korea.

An electrical noise is one of the key parameters determining the performance of modern electronic devices. However, it has been extremely difficult, if not impossible, to image localized noise sources or their activities in such devices. We report a "noise spectral imaging" strategy to map the activities of localized noise sources in graphene domains. Using this method, we could quantitatively estimate sheet resistances and noise source densities inside graphene domains, on domain boundaries and on the edge of graphene. The results show high activities of noise sources and large sheet resistance values at the domain boundary and edge of graphene. Additionally, we showed that the top layer in double-layer graphene had lower noises than single-layer graphene. This work provides valuable insights about the electrical noises of graphene. Furthermore, the capability to directly map noise sources in electronic channels can be a major breakthrough in electrical noise research in general.
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http://dx.doi.org/10.1021/acsnano.6b05288DOI Listing
November 2016

Broken-Symmetry Quantum Hall States in Twisted Bilayer Graphene.

Sci Rep 2016 12 1;6:38068. Epub 2016 Dec 1.

Department of Physics, Pohang University of Science and Technology, Pohang 37673, Korea.

Twisted bilayer graphene offers a unique bilayer two-dimensional-electron system where the layer separation is only in sub-nanometer scale. Unlike Bernal-stacked bilayer, the layer degree of freedom is disentangled from spin and valley, providing eight-fold degeneracy in the low energy states. We have investigated broken-symmetry quantum Hall (QH) states and their transitions due to the interplay of the relative strength of valley, spin and layer polarizations in twisted bilayer graphene. The energy gaps of the broken-symmetry QH states show an electron-hole asymmetric behaviour, and their dependence on the induced displacement field are opposite between even and odd filling factor states. These results strongly suggest that the QH states with broken valley and spin symmetries for individual layer become hybridized via interlayer tunnelling, and the hierarchy of the QH states is sensitive to both magnetic field and displacement field due to charge imbalance between layers.
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http://dx.doi.org/10.1038/srep38068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131475PMC
December 2016

Self-Renewal of Bone Marrow Stem Cells by Nanovesicles Engineered from Embryonic Stem Cells.

Adv Healthc Mater 2016 12 10;5(24):3148-3156. Epub 2016 Nov 10.

Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-Ro, Nam-gu, Pohang, Gyeong-buk, 37673, Republic of Korea.

Extracellular vesicles can enhance cell proliferation by stimulating signal transduction and delivering genetic materials, and thus may have applications in regenerative medicine and other therapeutic applications. The processes employed to isolate extracellular vesicles, however, are complex and achieve low yield. To overcome these obstacles, a large-scale, micropore device for generating extracellular vesicle-mimetic nanovesicles that have characteristics similar to those of extracellular vesicles is fabricated. The nanovesicles are generated through the self-assembly capability of cell membrane fragments in an aqueous solution. The nanovesicles enhance the proliferation of murine mesenchymal stem cells (MSCs), stimulate the signal pathway related to cell proliferation, and do not influence the characteristics of murine MSCs. Therefore, these nanovesicles could provide stable MSCs for regenerative medicine and other therapeutic applications.
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http://dx.doi.org/10.1002/adhm.201600810DOI Listing
December 2016