Publications by authors named "Changmo Hwang"

18 Publications

  • Page 1 of 1

Effect of Rho-Associated Kinase Inhibitor and Mesenchymal Stem Cell-Derived Conditioned Medium on Corneal Endothelial Cell Senescence and Proliferation.

Cells 2021 Jun 11;10(6). Epub 2021 Jun 11.

Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul 05505, Korea.

This study aims to obtain sufficient corneal endothelial cells for regenerative application. We examined the combinatory effects of Rho-associated kinase (ROCK) inhibitor Y-27632 and mesenchymal stem cell-derived conditioned medium (MSC-CM) on the proliferation and senescence of rabbit corneal endothelial cells (rCECs). rCECs were cultured in a control medium, a control medium mixed with either Y-27632 or MSC-CM, and a combinatory medium containing Y-27632 and MSC-CM. Cells were analyzed for morphology, cell size, nuclei/cytoplasmic ratio, proliferation capacity and gene expression. rCECs cultured in a combinatory culture medium showed a higher passage number, cell proliferation, and low senescence. rCECs on collagen type I film showed high expression of tight junction. The cell proliferation marker Ki-67 was positively stained either in Y-27632 or MSC-CM-containing media. Genes related to cell proliferation resulted in negligible changes in MKI67, CIP2A, and PCNA in the combinatory medium, suggesting proliferative capacity was maintained. In contrast, all of these genes were significantly downregulated in the other groups. Senescence marker β-galactosidase-positive cells significantly decreased in either MSC-CM and/or Y-27632 mixed media. Senescence-related genes downregulated LMNB1 and MAP2K6, and upregulated MMP2. Cell cycle checkpoint genes such as CDC25C, CDCA2, and CIP2A did not vary in the combinatory medium but were significantly downregulated in either ROCK inhibitor or MSC-CM alone. These results imply the synergistic effect of combinatory culture medium on corneal endothelial cell proliferation and high cell number. This study supports high potential for translation to the development of human corneal endothelial tissue regeneration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cells10061463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230597PMC
June 2021

Acetazolamide-eluting biodegradable tubular stent prevents pancreaticojejunal anastomotic leakage.

J Control Release 2021 Jul 10;335:650-659. Epub 2021 Jun 10.

Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea; Division of Hepatobiliary Pancreas Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea; Asan Medical Institute of Convergence Science and Technology (AMIST), Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea. Electronic address:

Postoperative pancreatic fistula at the early stage can lead to auto-digestion, which may delay the recovery of the pancreaticojejunal (PJ) anastomosis. The efficacy and safety of an acetazolamide-eluting biodegradable tubular stent (AZ-BTS) for the prevention of self-digestion and intra-abdominal inflammatory diseases caused by pancreatic juice leakage after PJ anastomosis in a porcine model were investigated. The AZ-BTS was successfully fabricated using a multiple dip-coating process. Then, the drug amount and release profile were analyzed. The therapeutic effects of AZ were examined in vitro using two kinds of pancreatic cancer cell lines, AsPC-1 and PANC-1. The efficacy of AZ-BTS was assessed in a porcine PJ leakage model, with animals were each assigned to a leakage group, a BTS group and an AZ-BTS group. The overall mortality rates in these three groups were 44.4%, 16.6%, and 0%, respectively. Mean α-amylase concentrations were significantly higher in the leakage and BTS groups than in the AZ-BTS group on day 2-5 (p < 0.05 each all). The luminal diameters and areas of the pancreatic duct were significantly larger in the leakage group than in the BTS and AZ-BTS groups (p < 0.05 each all). These findings indicate that AZ-BTS can significantly suppress intra-abdominal inflammatory diseases caused by pancreatic juice leakage and also prevent late stricture formation at the PJ anastomotic site in a porcine model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jconrel.2021.06.010DOI Listing
July 2021

Transplantation of human corneal limbal epithelial cell sheet harvested on synthesized carboxymethyl cellulose and dopamine in a limbal stem cell deficiency.

J Tissue Eng Regen Med 2021 02 10;15(2):139-149. Epub 2020 Dec 10.

Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

This study aimed to evaluate the efficacy and safety of transplantation with human corneal limbal epithelial (HCLE) cell sheets cultured on carboxymethyl cellulose (CMC)-dopamine (DA)-coated substrates and harvested via enzymatic digestion of CMC with cellulase in a rabbit animal model of limbal stem cell deficiency (LSCD). Synthesized CMC-DA was pretreated onto the surface of culture plates. Then, HCLE cells were cultured on precoated CMC-DA and HCLE cell sheets were harvested using cellulase-containing cell culture medium. HCLE cell sheets were evaluated using a live/dead assay, histological examination, and immunofluorescence staining. For in vivo assessment, HCLE cell sheets were transplanted in a rabbit model of LSCD for 2 weeks to determine the effectiveness of the repair. Primary culture of HCLE cells stained positively for p63, cytokeratin (CK)15, and CK12. HCLE cell sheets were generated with a well-preserved morphology and transparency ranging in size from 15 to 19 mm after cellulase-assisted cell sheet generation. HCLE cell sheets uniformly stained positively for human mitochondria, p63, CK15, CK12, CK3/2p, and zonula occludens (ZO)-1. HCLE cell sheet transplantation in a rabbit model of LSCD improved the corneal opacity and neovascularization scores. Transplanted HCLE cell sheets stained positively for p63 and CK12. Transplantation of HCLE cell sheets harvested on CMC-DA coating combined with cellulase is a safe and efficient procedure for corneal epithelial regeneration in a rabbit model of LSCD. This system could enable a promising strategy to regenerate corneal epithelium by transplantation in ocular surface disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/term.3159DOI Listing
February 2021

A Novel Biodegradable Tubular Stent Prevents Pancreaticojejunal Anastomotic Stricture.

Sci Rep 2020 01 30;10(1):1518. Epub 2020 Jan 30.

Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Stricture of pancreatic-enteric anastomoses is a major late complication of a pancreaticoduodenectomy for the treatment of a periampullary tumor and can lead to exocrine and endocrine insufficiency such as malnutrition and diabetes mellitus. We investigated the safety and efficacy of a biodegradable tubular stent (BTS) for preventing a pancreaticojejunostomy (PJ) anastomotic stricture in both a rat and porcine model. The BTS was manufactured using a terpolymer comprising poly p-dioxanone, trimethylene carbonate, and glycolide. A cohort of 42 rats was randomized into 7 groups of 6 animals each after BTS placement into the duodenum for the biodegradation assay. A total of 12 pigs were randomized equally into a control and BTS placement group. The effectiveness of the BTS was assessed by comparing radiologic images with histologic results. Surgical procedures and/or BTS placements were technically successful in all animals. The median mass losses of the removed BTS samples from the rat duodenum were 2.1, 6.8, 11.2, 19.4, 26.1, and 56.8% at 1, 2, 3, 4, 6, and 8 weeks, respectively. The BTS had completely degraded at 12 weeks in the rats. In the porcine PJ model, the mean luminal diameter and area of the pancreatic duct in the control group was significantly larger than in the BTS group (all p < 0.05). BTS placement thus appears to be safe and effective procedure for the prevention of PJ anastomotic stricture. These devices have the potential to be used as a temporary stent placement to treat pancreatic-enteric anastomoses, but further investigations are required for optimization in human.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-57271-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992790PMC
January 2020

Coaxial bioprinting of cell-laden vascular constructs using a gelatin-tyramine bioink.

Biomater Sci 2019 Nov 21;7(11):4578-4587. Epub 2019 Aug 21.

Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea. and Department of Convergence Medicine, University of Ulsan College of Medicine & Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.

Herein, three-dimensional (3D) bioprinting of engineered constructs with cell-laden biomaterials was investigated for the development of 3D tissue constructs in vitro. The present article proposes a simple coaxial-nozzle-based printing method using a one-step gelling gelatin bioink containing different cell types for vascular structure generation. First, a gelatin bioink prepolymer with a tyramine functional group was synthesized. To facilitate rapid gelation, polyethylene glycol (PEG) was introduced as a spacer between gelatin and tyramine. The gelatin-PEG-tyramine (GPT) prepolymer underwent enzymatic crosslinking, which yielded a higher gelation rate of up to 4.24 ± 0.08 s. Second, one-step bioprinting of a cell-laden tubular structure was demonstrated using a coaxial type extruder and the GPT bioink with human umbilical vein endothelial cells (HUVECs) with or without human dermal fibroblasts (HDFs). The printed no-cell GPT tube was demonstrated to possess a perfusable vascular structure. The extruded tube with HUVECs-in-GPT sheath configuration resulted in an endothelial cell-lined hollow structure and was maintained for up to 8 days in vitro. Additionally, the coaxially extruded tube with HUVECs-in-core (gelatin) and HDFs-in-GPT sheath (GPT) configuration exhibited a distribution of these two cell types along the tube axis. In the current study, it was demonstrated that a radial distribution of multiple vascular cells can be simply achieved using a synthetic GPT bioink combined with a coaxial nozzle printing system, serving as a proof-of-concept for one-step generation of vascular constructs. The rapid gelling bioink prepolymer, in combination with a coaxial bioprinter nozzle mechanism, has great potential for the development of designed, printed, and organized 3D tissue architecture vascularization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c8bm00618kDOI Listing
November 2019

In vitro lung cancer multicellular tumor spheroid formation using a microfluidic device.

Biotechnol Bioeng 2019 11 26;116(11):3041-3052. Epub 2019 Jul 26.

Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.

The purpose of this study was to demonstrate self-organizing in vitro multicellular tumor spheroid (MCTS) formation in a microfluidic system and to observe the behavior of MCTSs under controlled microenvironment. The employed microfluidic system was designed for simple and effective formation of MCTSs by generating nutrient and oxygen gradients. The MCTSs were composed of cancer cells, vascular endothelial cells, and type I collagen matrix to mimic the in vivo tumor microenvironment (TME). Cell culture medium was perfused to the microfluidic device loaded with MCTSs by a passive fluidic pump at a constant flow rate. The dose response to an MMPs inhibitor was investigated to demonstrate the effects of biochemical substances. The result of long-term stability of MCTSs revealed that continuous perfusion of cell culture medium is one of the major factors for the successful MCTS formation. A continuous flow of cell culture medium in the in vitro TME greatly affected both the proliferation of cancer cells in the micro-wells and the sustainability of the endothelial cell-layer integrity in the lumen of microfluidic channels. Addition of MMP inhibitor to the cell culture medium improved the stability of the collagen matrix by preventing the detachment and shrinkage of the collagen matrix surrounding the MCTSs. In summary, the present constant flow assisted microfluidic system is highly advantageous for long-term observation of the MCTS generation, tumorous tissue formation process and drug responses. MCTS formation in a microfluidic system may serve as a potent tool for studying drug screening, tumorigenesis and metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/bit.27114DOI Listing
November 2019

Embossed Membranes with Vascular Patterns Guide Vascularization in a 3D Tissue Model.

Polymers (Basel) 2019 May 2;11(5). Epub 2019 May 2.

Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Korea.

The vascularization of three-dimensional (3D) tissue constructs is necessary for transporting nutrients and oxygen to the component cells. In this study, a vacuum forming method was applied to emboss a vascular pattern on an electrospun membrane so that guided vascular structures could develop within the construct. Two- or six-layer constructs of electrospun membranes seeded with endothelial cells and pericytes were stacked and subcutaneously implanted into mice. Blood vessel formation in the implanted constructs with six alternating layers of flat membranes and membranes embossed with a blood vessel pattern was observed after two weeks of implantation. The formation of blood vessels was observed along the embossed blood vessel pattern in the structure of the embossed membrane laminated at four weeks and eight weeks. Vascular endothelial growth factor (VEGF) and angiopoietin 1 (Ang-1) were highly expressed in the vascularized structures. Therefore, we demonstrated that a structure capable of producing a desired blood vessel shape with electrospun membranes embossed with a blood vessel pattern can be manufactured, and that a variety of structures can be manufactured using electrospun membranes in the tissue engineering era.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/polym11050792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572394PMC
May 2019

Observation of Endothelial Cell-Assisted Vascularization in Pancreatic Cancer Xenograft Engineering.

Tissue Eng Regen Med 2018 Jun 3;15(3):275-285. Epub 2018 Feb 3.

1Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505 South Korea.

In this study, for better understanding of patient-derived xenograft (PDX) generation, angiogenic characteristics during PDX cancerous tissue generation was investigated with different initial cell seeding conditions in the hydrogel. We monitored the angiogenic changes during the formation of cancer cell line xenografts induced by endothelial cells. Our cancer tissue formation system was designed with the assistance of tissue engineering technology to mimic patient-derived xenograft formation. Endothelial cells and MIA PaCa-2 pancreatic carcinoma cells were encapsulated in fibrin gel at different mixing configurations and subcutaneously implanted into nude mice. To investigate the effect of the initial cancerous cell distribution in the fibrin gel, MIA PaCa-2 cells were encapsulated as a homogeneous cell distribution or as a cell aggregate, with endothelial cells homogeneously distributed in the fibrin gel. Histological observation of the explanted tissues after different implantation periods revealed three different stages: isolated vascular tubes, leaky blood vessels, and mature cancerous tissue formation. The engineered cancerous tissues had leaky blood vessels with low expression of the vascular tight junction marker CD31. Under our experimental conditions, complex cancer-like tissue formation was most successful when tumorous cells and endothelial cells were homogeneously mixed in the fibrin gel. The present study implies that tumorous xenograft tissue formation can be achieved with a low number of initial cells and that effective vascularization conditions can be attained with a limited volume of patient-derived cancer tissue. Endothelial cell-assisted vascularization can be a potent choice for the effective development of vascularized cancerous tissues for studying patient-derived xenografts, cancer angiogenesis, cancer metastasis, and anticancer drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13770-018-0113-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171679PMC
June 2018

Conjugation of carboxymethyl cellulose and dopamine for cell sheet harvesting.

Biomater Sci 2018 Dec;7(1):139-148

Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Republic of Korea.

In this study, we investigated the feasibility of enzymatic digestion of polysaccharides for cell sheet harvesting. Cellulose was digested using cellulase; in brief, cellulose was pre-coated under a confluent cell layer, and then enzymatic digestion of cellulose under the confluent cell layer enabled cell detachment with minimal cell damage, yielding cell sheets. For the surface adhesion of the cellulose, carboxymethyl cellulose (CMC) molecules were conjugated with dopamine (DA), and the synthesized CMC-DA was pre-treated onto the surface of the culture plates. Then, human mesenchymal stem cells (hMSCs) or corneal limbal epithelial cells (hCLEs) were cultured on the pre-coated CMC-DA and harvested using cellulase containing cell culture medium. Single hMSCs treated with cellulase showed higher proliferative activity, showing an aggregated morphology compared with trypsin-treated hMSCs. Additionally, hMSC sheets were detached from the pre-coated CMC-DA surface 10 min after cellulase treatment. Also, hCLE sheets were generated with a well-preserved morphology and transparency after cellulase-assisted cell sheet generation. These results demonstrate that the strategy of CMC-DA coating combined with cellulase enzymatic harvesting is an effective option for harvesting cell sheets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c8bm00971fDOI Listing
December 2018

Human Conjunctival Epithelial Sheets Grown on Poly(Lactic-Co-Glycolic) Acid Membranes and Cocultured With Human Tenon's Fibroblasts for Corneal Repair.

Invest Ophthalmol Vis Sci 2018 03;59(3):1475-1485

Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.

Purpose: We determine the feasibility of human conjunctival epithelial cells (hCjECs) on poly(lactic-co-glycolic) acid (PLGA) membranes for corneal epithelium regeneration. hCjECs on PLGA or polyester (PET) membranes with or without coculture of human Tenon's fibroblasts (hTFs) were compared in vitro, and to determine whether epithelial sheets grown on PLGA membranes can repair injured rabbit corneal epithelium by transplantation for 2 weeks in vivo.

Methods: Primary hCjECs were cultured on PLGA or the original PET membrane-based transwell inserts with or without coculture of hTFs on the floor of the culture plate. Cell behaviors, such as proliferation and differentiation, were compared. For in vivo assessment, the corneas of rabbits were burned, and PLGA-based epithelial sheets then were transplanted for 2 weeks before histologic staining was conducted and analyzed to determine the effectiveness of the repair.

Results: Primary human epithelial cells on the PLGA membrane showed an increased proliferation when cocultured with fibroblasts, which was confirmed by CCK-8 analysis, and upregulation of Ki67, with the expression of the epithelial marker CK19. The stratified squamous cell marker MUC1 and conjunctival cell marker MUC5AC also were expressed in the epithelial sheet. The epithelial defect in the burned corneas was decreased in the PLGA-based epithelial sheet treatment group (6.1% ± 1.6% of the area) compared to that in the no-treatment group (30.5% ± 6.3%) 2 weeks postoperatively.

Conclusions: We developed a coculture system using a human feeder cell layer and PLGA membrane-based transwell inserts to create human conjunctival epithelial sheets. This system represents a promising strategy to regenerate corneal epithelium by transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.17-22719DOI Listing
March 2018

Directional migration of mesenchymal stem cells under an SDF-1α gradient on a microfluidic device.

PLoS One 2017 8;12(9):e0184595. Epub 2017 Sep 8.

Department of Biomedical Engineering, Biomedical Science of Brain Korea 21, College of Medicine, Korea University, Seoul, Korea.

Homing of peripheral stem cells is regulated by one of the most representative homing factors, stromal cell-derived factor 1 alpha (SDF-1α), which specifically binds to the plasma membrane receptor CXCR4 of mesenchymal stem cells (MSCs) in order to initiate the signaling pathways that lead to directional migration and homing of stem cells. This complex homing process and directional migration of stem cells have been mimicked on a microfluidic device that is capable of generating a chemokine gradient within the collagen matrix and embedding endothelial cell (EC) monolayers to mimic blood vessels. On the microfluidic device, stem cells showed directional migration toward the higher concentration of SDF-1α, whereas treatment with the CXCR4 antagonist AMD3100 caused loss of directionality of stem cells. Furthermore, inhibition of stem cell's main migratory signaling pathways, Rho-ROCK and Rac pathways, caused blockage of actomyosin and lamellipodia formation, decreasing the migration distance but maintaining directionality. Stem cell homing regulated by SDF-1α caused directional migration of stem cells, while the migratory ability was affected by the activation of migration-related signaling pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0184595PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5590985PMC
October 2017

Multilayered Engineered Tissue Sheets for Vascularized Tissue Regeneration.

Tissue Eng Regen Med 2017 Aug 3;14(4):371-381. Epub 2017 Jul 3.

1Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505 Korea.

A major hurdle in engineering thick and laminated tissues such as skin is how to vascularize the tissue. This study introduces a promising strategy for generating multi-layering engineered tissue sheets consisting of fibroblasts and endothelial cells co-seeded on highly micro-fibrous, biodegradable polycaprolactone membrane. Analysis of the conditions for induction of the vessels showed that addition of endothelial cell sheets into the laminated structure increases the number of incorporated cells and promotes primitive endothelial vessel growth. analysis of 11-layered constructs showed that seeding a high number of endothelial cells resulted in better cell survival and vascularization 4 weeks after implantation. Within one week after implantation , red blood cells were detected in the middle section of three-layered engineered tissue sheets composed of polycaprolactone/collagen membranes. Our engineered tissue sheets have several advantages, such as easy handling for cell seeding, manipulation by stacking each layer, a flexible number of cells for next-step applications and versatile tissue regeneration, and automated thick tissue generation with proper vascularization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13770-017-0049-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171602PMC
August 2017

Quantification of the Radiopacity of Onyx during Embolization.

Neurointervention 2017 Mar 6;12(1):3-10. Epub 2017 Mar 6.

Department of Radiology, Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Purpose: Onyx has been successfully applied in the treatment of various neurovascular lesions. However, some experience is required to get accustomed to its unpredictable fluoroscopic visibility during injection. This study aimed to evaluate the characteristics of radiopacity change in a simulated embolization procedure.

Materials And Methods: Using a bench-top Onyx injection experiment simulating a typical brain arteriovenous malformation embolization, nine cycles of casting modes (continuous injection) and plugging modes (injection with intermittent pauses) were performed. Radiodensity of Onyx droplets collected from the microcatheter tip and the distal head portion of the microcatheter were measured as time lapsed. Distribution of droplet radiodensity (radiodensity) and distribution of radiographic grade (grade) were analyzed and compared by repeated measurements.

Results: Within-group analysis revealed no significant radiodensity change with time (P>0.05). The radiodensity was significantly higher in the casting mode than in the plugging mode (P<0.01). The lateral radiograph of the microcatheter showed higher radiopacity (P<0.01) and better evenness (P<0.01) in the casting mode than in the plugging mode. A significant difference in microcatheter attenuation (both radiographic grade mean and SD; P<0.01) was noted between the two modes. Radiodensity had a significant influence on the radiopacity and radiopacity evenness of the microcatheter.

Conclusion: The radiopacity of the Onyx can vary significantly over time because of early precipitation of tantalum powder. Radiopacity decreased significantly during plugging modes, characterized by pauses between injections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5469/neuroint.2017.12.1.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355458PMC
March 2017

Fracture and migration of a retained wire into the thoracic cavity after endovascular neurointervention: report of 2 cases.

J Neurosurg 2017 Feb 18;126(2):354-359. Epub 2016 Mar 18.

Departments of 1 Radiology and Research Institute of Radiology.

Although extremely rare, retention of foreign bodies such as microcatheters or micro guidewires can occur during various neurovascular procedures due to gluing of the microcatheter tip or entanglement of the micro guidewire tip with intravascular devices. The authors have experienced 2 cases of irresolvable wire retention, one after flow diverter placement for a left cavernous internal carotid artery aneurysm and the other after intracranial stenting for acute basilar artery occlusion. The first patient presented 6 weeks after her procedure with right lung parenchymal hemorrhage due to direct piercing of the lung parenchyma after the retained wire fractured and migrated out of the aortic arch. The second patient presented 4 years after his procedure with pneumothorax due to migration of the fractured guidewire segment into the right thoracic cavity. In this report, the authors discuss the possible mechanisms of these unusual complications and how to prevent delayed consequences from a retained intravascular metallic wire.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2015.12.JNS152381DOI Listing
February 2017

Surgical and Oncological Factors Affecting the Successful Engraftment of Patient-derived Xenografts in Pancreatic Ductal Adenocarcinoma.

Anticancer Res 2016 Feb;36(2):517-21

Departments of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Songpa-gu, Seoul, Republic of Korea Asan Institute for Life Sciences, University of Ulsan College of Medicine and Asan Medical Center, Songpa-gu, Seoul, Republic of Korea

Background: To effectively use pancreatic cancer patient-derived xenograft (PDX) models in translational research, successful PDX engraftment of surgical specimens in immune-deficient mice is needed.

Materials And Methods: A total of 102 patients underwent pancreatic cancer resection using various procedures. Tumor tissue from all patents was implanted subcutaneously into mice. Tumor engraftment and growth in mice were determined. Engraftment was tested for correlation with operation type, time, tumor size, and oncogene expression using immunohistoculture.

Results: Multivariate analysis showed that a tumor size of more than 3.5 cm in the patient was a significant factor related to successful PDX engraftment. In contrast, there was no correlation of engraftment with surgical procedure, time needed to remove the specimen, tumor differentiation, lymph node metastasis, and protein expression of p53, Receptor tyrosine-protein kinase erbB-2 (CERBB2), or deleted in pancreatic carcinoma locus 4 (DPC4).

Conclusion: A minimum tumor size in the patient is an important factor for successful tumor engraftment.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2016

Inhibition of Rho-Associated Protein Kinase Increases the Angiogenic Potential of Mesenchymal Stem Cell Aggregates via Paracrine Effects.

Tissue Eng Part A 2016 Feb 21;22(3-4):233-43. Epub 2016 Jan 21.

1 Department of Biomedical Engineering, College of Medicine, Korea University , Seoul, Korea.

The aggregation of multiple cells, such as mesenchymal condensation, is an important biological process in skeletal muscle development, osteogenesis, and adipogenesis. Due to limited in vivo study model systems, a simple and effective in vitro three-dimensional (3D) aggregation system is required to study the mechanisms of multicellular aggregation and its applications. We first generated controlled mesenchymal stem cell (MSC) aggregates using a bioprinting technique to monitor their aggregation and sprouting. We induced the angiogenic potential of the MSCs through chemical inhibition of the Rho/Rho-associated protein kinase (ROCK) pathway, which led to hairy sprouting in the aggregates. The angiogenic potential of this 3D construct was then tested by subcutaneously implanting the Matrigel with 3D MSC aggregates in a rat. Treatment of 3D MSCs with the ROCK inhibitor, Y27632, increased their angiogenic activity in vivo. The gene expressions and histological staining indicated that angiogenesis and neovascularization were mainly regulated by the paracrine factors secreted from human 3D MSC constructs. Our results demonstrate the enhancement of the angiogenic potential of the MSC constructs through the secretion of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) by the inhibition of the Rho/ROCK pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/ten.TEA.2015.0289DOI Listing
February 2016

Compliant neurovascular balloon catheters may not be compatible with liquid embolic materials: intraprocedural rupture of the protecting balloon during tumor embolization using n-butyl cyanoacrylate and lipiodol mixture.

J Neurointerv Surg 2015 Oct 27;7(10):740-3. Epub 2014 Aug 27.

Department of Radiology, Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

Background: Simultaneous use of balloon catheters with embolic materials can cause unwanted rupture of the balloon occlusion catheters, which might cause a serious problem. Therefore, knowledge of the compatibility of occlusion balloon catheters with liquid embolic materials is important in various interventional procedures.

Objective: To determine the compatibility of occlusion balloon catheters with commonly used embolic materials in vitro.

Methods: We used three types of occlusion balloon catheters (Scepter C, Microvention, Tustin, California, USA; Hyperform, Covidien, Irvine, California, USA; and Ascent, Codman Neurovascular, Raynham, Massachusetts, USA) to test their tolerances to Lipiodol, n-butyl cyanoacrylate (NBCA; Histoacryl; B Braun, Melsungen, Germany), and dimethyl sulfoxide (DMSO) with Onyx. The balloon was inflated just as it is in an endovascular procedure, then put on a Petri dish to observe its morphological change after one drop of liquid embolic material was added using a 1 mL syringe. The presence of rupture and the time to rupture were evaluated by constant video monitoring. Additionally, we observed morphological changes of the balloon catheter surface after contact with embolic materials with a scanning electron microscope.

Results: Lipiodol or a 33% NBCA-Lipiodol mixture dropping onto the three types of balloon catheter resulted in ruptures of all three. All three types of balloon catheter were tolerant to NBCA and to DMSO followed by Onyx.

Conclusions: Glue embolization should not be performed with all three kinds of balloon catheter on the market, but DMSO and Onyx are compatible with those balloon catheters.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/neurintsurg-2014-011331DOI Listing
October 2015

Rapid generation of biologically relevant hydrogels containing long-range chemical gradients.

Adv Funct Mater 2010 ;20(1):131-137

Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA; State Key Laboratory of Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China.

Many biological processes are regulated by gradients of bioactive chemicals. Thus, the generation of materials with embedded chemical gradients may be beneficial for understanding biological phenomena and generating tissue-mimetic constructs. Here we describe a simple and versatile method to rapidly generate materials containing centimeter-long gradients of chemical properties in a microfluidic channel. The formation of chemical gradient was initiated by a passive-pump-induced forward flow and further developed during an evaporation-induced backward flow. The gradient was spatially controlled by the backward flow time and the hydrogel material containing the gradient was synthesized via photopolymerization. Gradients of a cell-adhesion ligand, Arg-Gly-Asp-Ser (RGDS), was incorporated in the poly(ethylene glycol)-diacrylate (PEG-DA) hydrogels to test the response of endothelial cells. The cells attached and spread along the hydrogel material in a manner consistent with the RGDS gradient profile. A hydrogel containing PEG-DA concentration gradient and constant RGDS concentration was also generated. The morphology of cells cultured on such hydrogel changed from round in the lower PEG-DA concentration regions to well-spread in the higher PEG-DA concentration regions. This approach is expected to be a valuable tool to investigate the cell-material interactions in a simple and high-throughput manner and to design graded biomimetic materials for tissue engineering applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adfm.200901311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834245PMC
January 2010
-->