Chung-Hee Sonn - Academia.edu (original) (raw)

Papers by Chung-Hee Sonn

Research paper thumbnail of RESEARCH ARTICLE Effect of Donor Age on the Proportion of Mesenchymal Stem Cells Derived from

The characteristics of anterior cruciate ligament (ACL)-derived mesenchymal stem cells (MSCs), su... more The characteristics of anterior cruciate ligament (ACL)-derived mesenchymal stem cells (MSCs), such as proportion and multilineage potential, can be affected by donor age. How-ever, the qualitative and quantitative features of ACL MSCs isolated from younger and older individuals have not yet been compared directly. This study assessed the phenotypic and functional differences in ACL-MSCs isolated from younger and older donors and evaluated the correlation between ACL-MSC proportion and donor age. Torn ACL remnants were har-vested from 36 patients undergoing ACL reconstruction (young: 29.67 ± 10.92 years) and 33 undergoing TKA (old: 67.96 ± 5.22 years) and the proportion of their MSCs were mea-sured. The mean proportion of MSCs was slightly higher in older ACL samples of the TKA group than of the younger ACL reconstruction group (19.69 ± 8.57 % vs. 15.33 ± 7.49%, p = 0.024), but the proportions of MSCs at passages 1 and 2 were similar. MSCs from both groups possessed comparable multi...

Research paper thumbnail of MethA Fibrosarcoma Cells Expressing Membrane-Bound Forms of IL-2 Enhance Antitumor Immunity

Journal of Microbiology and Biotechnology, 2006

Tumor cells genetically engineered to secrete cytokines are effective in tumor therapy, but vario... more Tumor cells genetically engineered to secrete cytokines are effective in tumor therapy, but various unexpected side effects are observed, which may result from the bulk activation of various bystander cells. In this study, we tested tumor vaccines expressing various membrane-bound forms of IL-2 (mbIL-2) on MethA fibrosarcoma cells to focus antitumor immune responses to CTL. Chimeric forms of IL-2 with whole CD4, deletion forms of CD4, and TNF were expressed on the tumor cell surface, respectively. Tumor clones expressing mbIL-2 or secretory form of IL-2 were able to support the cell growth of CTLL-2, an IL-2-dependent T cell line, and the proliferation of spleen cells from 2C TCR transgenic mice that are responsive to the p2Ca/L d MHC class I complex. Expression of mbIL-2 on tumor cells reduced the tumorigenicity of tumor cells, and the mice that once rejected the live IL-2/ TNF tumor close acquired systemic immunity against wild-type MethA cells. The IL-2/TNF clone was inferior to ...

Research paper thumbnail of Ginseng extract reduces fasting glucose level in blood and improves glucose tolerance as prophylaxis in a mouse type 1 diabetes model

Research paper thumbnail of Osteo-Compatibility of 3D Titanium Porous Coating Applied by Direct Energy Deposition (DED) for a Cementless Total Knee Arthroplasty Implant: In Vitro and In Vivo Study

Journal of Clinical Medicine, 2020

Direct energy deposition (DED) technology has gained increasing attention as a new implant surfac... more Direct energy deposition (DED) technology has gained increasing attention as a new implant surface technology that replicates the porous structure of natural bones facilitating osteoblast colonization and bone ingrowth. However, concerns have arisen over osteolysis or chronic inflammation that could be caused by Cobalt-chrome (CoCr) alloy and Titanium (Ti) nanoparticles produced during the fabrication process. Here, we evaluated whether a DED Ti-coated on CoCr alloy could improve osteoblast colonization and osseointegration in vitro and in vivo without causing any significant side effects. Three types of implant CoCr surfaces (smooth, sand-blasted and DED Ti-coated) were tested and compared. Three cell proliferation markers and six inflammatory cytokine markers were measured using SaOS2 osteoblast cells. Subsequently, X-ray and bone histomorphometric analyses were performed after implantation into rabbit femur. There were no differences between the DED group and positive control in ...

Research paper thumbnail of Titanium Porous Coating Using 3D Direct Energy Deposition (DED) Printing for Cementless TKA Implants: Does It Induce Chronic Inflammation?

Materials, 2020

Because of the recent technological advances, the cementless total knee arthroplasty (TKA) implan... more Because of the recent technological advances, the cementless total knee arthroplasty (TKA) implant showed satisfactory implant survival rate. Newly developed 3D printing direct energy deposition (DED) has superior resistance to abrasion as compared to traditional methods. However, there is still concern about the mechanical stability and the risk of osteolysis by the titanium (Ti) nanoparticles. Therefore, in this work, we investigated whether DED Ti-coated cobalt-chrome (CoCr) alloys induce chronic inflammation reactions through in vitro and in vivo models. We studied three types of implant surfaces (smooth, sand-blasted, and DED Ti-coated) to compare their inflammatory reaction. We conducted the in vitro effect of specimens using the cell counting kit-8 (CCK-8) assay and an inflammatory cytokine assay. Subsequently, in vivo analysis of the immune profiling, cytokine assay, and histomorphometric evaluation using C57BL/6 mice were performed. There were no significant differences in ...

Research paper thumbnail of Corrigendum: Circulating Aneuploid Cells Detected in the Blood of Patients with Infectious Lung Diseases

The Korean Journal of Thoracic and Cardiovascular Surgery, 2017

Research paper thumbnail of Detection of circulating tumor cells in patients with non-small cell lung cancer using a size-based platform

Oncology letters, 2017

The detection of circulating tumor cells (CTCs) is limited by the rarity of these cells in the pe... more The detection of circulating tumor cells (CTCs) is limited by the rarity of these cells in the peripheral blood of patients with cancer. Understanding tumor biology may be useful in the development of novel therapeutic strategies for patients with lung cancer. The present study evaluated a novel size-based filtration platform for enriching CTCs from patients with lung cancer. Blood samples were obtained from 82 patients with lung cancer for CTC analysis. CTC enrichment by size-based filtration was performed on 5-ml blood samples. The collected cells were detected by immunofluorescence using monoclonal anti-human antibodies against protein tyrosine phosphatase, receptor type C (CD45) and epithelial cell adhesion molecule (EpCAM; an epithelial cell marker), as well as a DAPI nucleic acid stain. CTCs were detected in 57 patients (69.5%) using the size-based filtration platform. The mean CTC counts, defined as the number of cells with DAPI-positive, CD45-negative and EpCAM-positive stai...

Research paper thumbnail of Circulating Aneuploid Cells Detected in the Blood of Patients with Infectious Lung Diseases

The Korean journal of thoracic and cardiovascular surgery, 2017

The identification of circulating tumor cells (CTCs) is clinically important for diagnosing cance... more The identification of circulating tumor cells (CTCs) is clinically important for diagnosing cancer. We have previously developed a size-based filtration platform followed by epithelial cell adhesion molecule immunofluorescence staining for detecting CTCs. To characterize CTCs independently of cell surface protein expression, we incorporated a chromosomal fluorescence in situ hybridization (FISH) assay to detect abnormal copy numbers of chromosomes in cells collected from peripheral blood samples by the size-based filtration platform. Aneuploid cells were detected in the peripheral blood of patients with lung cancer. Unexpectedly, aneuploid cells were also detected in the control group, which consisted of peripheral blood samples from patients with benign lung diseases, such as empyema necessitatis and non-tuberculous mycobacterial lung disease. These findings suggest that chromosomal abnormalities are observed not only in tumor cells, but also in benign infectious diseases. Thus, ou...

Research paper thumbnail of Investigation of influence of Proteus mirabilis LPS polysaccharide part on the murine immune cells activation

Archivum immunologiae et therapiae experimentalis, 1999

The biological activities were investigated of Proteus mirabilis lipopolysaccharides (LPSs) and t... more The biological activities were investigated of Proteus mirabilis lipopolysaccharides (LPSs) and their fragments, namely, the induction of nitric oxide (NO) and interleukin 1 (IL-1) synthesis by murine macrophages and the proliferation of murine spleen cells. The O-specific polysaccharide (F1), core oligosaccharide (F2) and lipid A were as effective as intact LPS in stimulating murine macrophages to produce NO. IL-1 synthesis was also induced by all studied types of endotoxins (S, Ra, Re) and partial structures, however F1, F2 and lipid A fractions required the presence of serum. In contrast to LPS, the O-specific polysaccharide, core oligosaccharide and lipid A were not able to induce the blast response of murine non-adherent splenocytes.

Research paper thumbnail of Effect of donor age on the proportion of mesenchymal stem cells derived from anterior cruciate ligaments

PloS one, 2015

The characteristics of anterior cruciate ligament (ACL)-derived mesenchymal stem cells (MSCs), su... more The characteristics of anterior cruciate ligament (ACL)-derived mesenchymal stem cells (MSCs), such as proportion and multilineage potential, can be affected by donor age. However, the qualitative and quantitative features of ACL MSCs isolated from younger and older individuals have not yet been compared directly. This study assessed the phenotypic and functional differences in ACL-MSCs isolated from younger and older donors and evaluated the correlation between ACL-MSC proportion and donor age. Torn ACL remnants were harvested from 36 patients undergoing ACL reconstruction (young: 29.67 ± 10.92 years) and 33 undergoing TKA (old: 67.96 ± 5.22 years) and the proportion of their MSCs were measured. The mean proportion of MSCs was slightly higher in older ACL samples of the TKA group than of the younger ACL reconstruction group (19.69 ± 8.57% vs. 15.33 ± 7.49%, p = 0.024), but the proportions of MSCs at passages 1 and 2 were similar. MSCs from both groups possessed comparable multiline...

Research paper thumbnail of Ethanol-dispersed polymer nanofiber net for highly-selective capture of lymph node CD4+ T cells

Research paper thumbnail of Synovial fluid CD34− CD44+ CD90+ mesenchymal stem cell levels are associated with the severity of primary knee osteoarthritis

Osteoarthritis and Cartilage, 2012

Research paper thumbnail of Augmentation of natural cytotoxicity by chronic low-dose ionizing radiation in murine natural killer cells primed by IL-2

Journal of Radiation Research, 2012

The possible beneficial effects of chronic low-dose irradiation (LDR) and its mechanism of action... more The possible beneficial effects of chronic low-dose irradiation (LDR) and its mechanism of action in a variety of pathophysiological processes such as cancer are a subject of intense investigation. While animal studies involving long-term exposure to LDR have yielded encouraging results, the influence of LDR at the cellular level has been less well defined. We reasoned that since natural killer (NK) cells constitute an early responder to exogenous stress, NK cells may reveal sentinel alterations in function upon exposure to LDR. When purified NK cells received LDR at 4.2 mGy/h for a total of 0.2 Gy in vitro, no significant difference in cell viability was observed. Likewise, no functional changes were detected in LDR-exposed NK cells, demonstrating that LDR alone was insufficient to generate changes at the cellular level. Nonetheless, significant augmentation of cytotoxic, but not proliferative, function was detected when NK cells were stimulated with low-dose IL-2 prior to irradiation. This enhancement of NK cytotoxicity was not due to alterations in NK-activating receptors, NK1.1, NKG2D, CD69 and 2B4, or changes in the rate of early or late apoptosis. Therefore, LDR, in the presence of suboptimal cytokine levels, can facilitate anti-tumor cytotoxicity of NK cells without influencing cellular proliferation or apoptosis. Whether these results translate to in vivo consequences remains to be seen; however, our data provide initial evidence that exposure to LDR can lead to subtle immune-enhancing effects on NK cells and may explain, in part, the functional basis underlying, diverse beneficial effects seen in the animals chronically exposed to LDR.

Research paper thumbnail of Clusterin synergizes with IL-2 for the expansion and IFN-  production of natural killer cells

Journal of Leukocyte Biology, 2010

CLU is a secreted, multifunctional protein implicated in several immunologic and pathologic condi... more CLU is a secreted, multifunctional protein implicated in several immunologic and pathologic conditions. As the level of serum CLU was shown to be elevated during inflammatory responses, we questioned if CLU might interact with circulating lymphocytes leading to functional consequences. To assess this possibility directly, mouse splenocytes and purified NK cells were cultured with varying dose of CLU, and its effect on cell proliferation was examined. Our data showed that CLU up-regulated DNA synthesis and expansion of NK cells significantly in response to a suboptimal, but not maximal, dose of IL-2, and CLU alone did not exhibit such effects. This CLU-mediated synergy required the co-presence of CLU at the onset of IL-2 stimulation and needed a continuous presence during the rest of the culture. Importantly, NK cells stimulated with CLU showed increased formation of cell clusters and a CD69 activation receptor, representing a higher cellular activation status compared with those from the control group. Furthermore, these NK cells displayed elevated IFN-γ production upon RMA/S tumor target exposures, implying that CLU regulates not only NK cell expansion but also effector function of NK cells. Collectively, our data present a previously unrecognized function of CLU as a novel regulator of NK cells via providing costimulation required for cell proliferation and IFN-γ secretion. Therefore, the role of CLU on NK cells should be taken into consideration for the previously observed, diverse functions of CLU in chronic inflammatory and autoimmune conditions.

Research paper thumbnail of Korean red ginseng (Panax ginseng) ameliorates type 1 diabetes and restores immune cell compartments

Journal of Ethnopharmacology, 2012

Ethnopharmacological relevance: Historical records reveal that in traditional medicine, a disease... more Ethnopharmacological relevance: Historical records reveal that in traditional medicine, a disease similar to diabetes was treated with ginseng. Korean red ginseng has been considered beneficial as a dietary supplement for its anti-diabetic potential. Aim: This study was designed to investigate the prophylactic potential of Korean red ginseng (KRG) extract (Panax ginseng C.A. Meyer Radix Rubra) in a well-established mouse model of Type 1 diabetes (T1D). Materials and methods: The prophylactic effect of KRG extract was evaluated in mice fed with KRG extract for two weeks prior to induction of diabetes by streptozotocin (STZ) administration. Glucose levels and glucose challenge test results of KRG-treated diabetic mice were compared to those of untreated diabetic mice and healthy control mice. Examination of the immune compartments in lymphoid organs and immunohistochemical staining of pancreas for islet cell morphology and insulin producing beta cells were performed. Results: KRG extract significantly lowered blood glucose levels to an average of 250 mg/dl from 350 mg/dl and improved glucose challenge testing when applied as prophylaxis. Histological findings indicated that KRG extract protected against STZ-induced destruction of pancreatic tissue and restored insulin secretion. Strikingly, this effect was accompanied by restoration of lymphocytes in secondary lymphoid organs, suggesting that KRG extract facilitated immune homeostasis. Conclusion: This is the first report to demonstrate the prophylactic function of KRG extract in ameliorating the hyperglycemia of T1D. Immune compartments of diabetic mice were found to be preserved in KRG-treated mice suggesting that Korean red ginseng may benefit T1D patients, not only for its hypoglycemic but also for its immunomodulatory effects.

Research paper thumbnail of Tumor cells expressing membrane-bound form of IL-4 induce antitumor immunity

Gene Therapy, 2000

Local cytokine concentrations are required for inhibition of tumor growth with less toxic side-ef... more Local cytokine concentrations are required for inhibition of tumor growth with less toxic side-effects. However, genetically engineered tumor cells secreting cytokines still induce toxicity and activate bystander cells. To circumvent such problems, membrane-bound forms of IL-4 (IL-4m) were expressed on MethA fibrosarcoma tumor cells. Chimeric forms of IL-4 with the type I transmembrane protein CD4 or type II transmembrane protein TNF were designed to express IL-4 in opposite orientations on the tumor cell surface. The IL-4m on tumor clones was able to support cell growth of the IL-4 dependent cytotoxic cell line (CT.4S) and

Research paper thumbnail of Erratum: Oncolytic adenovirus co-expressing IL-12 and IL-18 improves tumor-specific immunity via differentiation of T cells expressing IL-12Rβ2 or IL-18Rα

Research paper thumbnail of Impact of chronicity of injury on the proportion of mesenchymal stromal cells derived from anterior cruciate ligaments

Cytotherapy, 2014

Background aims. The graft-healing potential of mesenchymal stromal cells (MSCs) derived from the... more Background aims. The graft-healing potential of mesenchymal stromal cells (MSCs) derived from the remnants of ruptured anterior cruciate ligaments (ACLs) after ACL reconstruction may depend on the chronicity of the injury. The aim of this study was to assess the quantitative and phenotypic differences between MSCs isolated from ACL remnants in patients with (sub) acute and chronic tearing. Methods. Torn ACL remnants were harvested during ACL reconstruction from 41 patients, 24 with (sub)acute ACL (<6 months from injury to surgery) and 17 with chronic ACL (time interval >6 months) tears. MSCs isolated from these samples were assessed for quantitative and phenotypic differences, and the correlation between the proportion of MSCs and the chronicity of ACL tear was evaluated. Results. At passage 0, the mean proportion of MSCs (CD34 À , CD44 þ , CD90 þ and CD105 þ) was higher in (sub)acute than in chronic ACL tear samples (20.69% AE 7.82% versus 9.85% AE 8.01%, P < 0.001). At passages 1 and 2, however, MSC proportions did not differ significantly in the two groups. Time interval showed a negative correlation with MSC proportion only at passage 0 (r ¼ À0.505, P < 0.001). The optimal cutoff value for time from injury to surgery yielding <10% freshly isolated ACL-MSCs, a percentage expected to have low tissue healing potential, was 23.5 months. Conclusions. The proportion of freshly isolated MSCs was higher in samples from patients with (sub)acute tearing than in chronic ACL tearing and negatively correlated with the time interval between trauma and surgery.

Research paper thumbnail of Isolation and expansion of synovial CD34−CD44+CD90+mesenchymal stem cells: comparison of an enzymatic method and a direct explant technique

Connective Tissue Research, 2010

Synovium-derived mesenchymal stem cells (MSCs) offer a promising therapeutic option for cartilage... more Synovium-derived mesenchymal stem cells (MSCs) offer a promising therapeutic option for cartilage regeneration. The conventional method of MSC isolation involves single-cell suspensions using collagenases. Recently, a nonenzymatic explant technique was developed to isolate MSCs. We compared these techniques in the isolation of functional MSCs. MSCs were isolated from human fibrous and adipose synovium of osteoarthritic patients using explants or enzymatic methods. Total cell number, percentage of MSCs, and surface marker expression of MSCs were measured following expansion. Multipotentiality was determined using a MSC functional identification kit. MSCs isolated from fibrous or adipose synovium using these two techniques expressed similar levels of the surface markers CD44, CD90, and CD105, and displayed similar multipotentiality in generating adipocytes, osteoblasts, and chondrocytes. Total cell number and number of CD34(-)CD44(+)CD90(+) MSCs after 10-day expansion were similar in each culture, regardless of the source and method used, although the percentage of MSCs was slightly higher in explant cultures. There were no correlations between MSC yield and patient age, Hospital for Special Surgery score, and degree of deformity under all culture conditions. Both the enzymatic and explant techniques yielded similar yields of MSCs with similar characteristics. Because the explant technique is simpler and less invasive, it may be preferred over enzymatic techniques for isolating MSCs from the synovium of osteoarthritic patients for cartilage regeneration.

Research paper thumbnail of API5 Confers Tumoral Immune Escape through FGF2-Dependent Cell Survival Pathway

Cancer Research, 2014

Identifying immune escape mechanisms used by tumors may define strategies to sensitize them to im... more Identifying immune escape mechanisms used by tumors may define strategies to sensitize them to immunotherapies to which they are otherwise resistant. In this study, we show that the antiapoptotic gene API5 acts as an immune escape gene in tumors by rendering them resistant to apoptosis triggered by tumor antigen-specific T cells. Its RNAi-mediated silencing in tumor cells expressing high levels of API5 restored antigen-specific immune sensitivity. Conversely, introducing API5 into API5low cells conferred immune resistance. Mechanistic investigations revealed that API5 mediated resistance by upregulating FGF2 signaling through a FGFR1/PKCδ/ERK effector pathway that triggered degradation of the proapoptotic molecule BIM. Blockade of FGF2, PKCδ, or ERK phenocopied the effect of API5 silencing in tumor cells expressing high levels of API5 to either murine or human antigen-specific T cells. Our results identify a novel mechanism of immune escape that can be inhibited to potentiate the ef...

Research paper thumbnail of RESEARCH ARTICLE Effect of Donor Age on the Proportion of Mesenchymal Stem Cells Derived from

The characteristics of anterior cruciate ligament (ACL)-derived mesenchymal stem cells (MSCs), su... more The characteristics of anterior cruciate ligament (ACL)-derived mesenchymal stem cells (MSCs), such as proportion and multilineage potential, can be affected by donor age. How-ever, the qualitative and quantitative features of ACL MSCs isolated from younger and older individuals have not yet been compared directly. This study assessed the phenotypic and functional differences in ACL-MSCs isolated from younger and older donors and evaluated the correlation between ACL-MSC proportion and donor age. Torn ACL remnants were har-vested from 36 patients undergoing ACL reconstruction (young: 29.67 ± 10.92 years) and 33 undergoing TKA (old: 67.96 ± 5.22 years) and the proportion of their MSCs were mea-sured. The mean proportion of MSCs was slightly higher in older ACL samples of the TKA group than of the younger ACL reconstruction group (19.69 ± 8.57 % vs. 15.33 ± 7.49%, p = 0.024), but the proportions of MSCs at passages 1 and 2 were similar. MSCs from both groups possessed comparable multi...

Research paper thumbnail of MethA Fibrosarcoma Cells Expressing Membrane-Bound Forms of IL-2 Enhance Antitumor Immunity

Journal of Microbiology and Biotechnology, 2006

Tumor cells genetically engineered to secrete cytokines are effective in tumor therapy, but vario... more Tumor cells genetically engineered to secrete cytokines are effective in tumor therapy, but various unexpected side effects are observed, which may result from the bulk activation of various bystander cells. In this study, we tested tumor vaccines expressing various membrane-bound forms of IL-2 (mbIL-2) on MethA fibrosarcoma cells to focus antitumor immune responses to CTL. Chimeric forms of IL-2 with whole CD4, deletion forms of CD4, and TNF were expressed on the tumor cell surface, respectively. Tumor clones expressing mbIL-2 or secretory form of IL-2 were able to support the cell growth of CTLL-2, an IL-2-dependent T cell line, and the proliferation of spleen cells from 2C TCR transgenic mice that are responsive to the p2Ca/L d MHC class I complex. Expression of mbIL-2 on tumor cells reduced the tumorigenicity of tumor cells, and the mice that once rejected the live IL-2/ TNF tumor close acquired systemic immunity against wild-type MethA cells. The IL-2/TNF clone was inferior to ...

Research paper thumbnail of Ginseng extract reduces fasting glucose level in blood and improves glucose tolerance as prophylaxis in a mouse type 1 diabetes model

Research paper thumbnail of Osteo-Compatibility of 3D Titanium Porous Coating Applied by Direct Energy Deposition (DED) for a Cementless Total Knee Arthroplasty Implant: In Vitro and In Vivo Study

Journal of Clinical Medicine, 2020

Direct energy deposition (DED) technology has gained increasing attention as a new implant surfac... more Direct energy deposition (DED) technology has gained increasing attention as a new implant surface technology that replicates the porous structure of natural bones facilitating osteoblast colonization and bone ingrowth. However, concerns have arisen over osteolysis or chronic inflammation that could be caused by Cobalt-chrome (CoCr) alloy and Titanium (Ti) nanoparticles produced during the fabrication process. Here, we evaluated whether a DED Ti-coated on CoCr alloy could improve osteoblast colonization and osseointegration in vitro and in vivo without causing any significant side effects. Three types of implant CoCr surfaces (smooth, sand-blasted and DED Ti-coated) were tested and compared. Three cell proliferation markers and six inflammatory cytokine markers were measured using SaOS2 osteoblast cells. Subsequently, X-ray and bone histomorphometric analyses were performed after implantation into rabbit femur. There were no differences between the DED group and positive control in ...

Research paper thumbnail of Titanium Porous Coating Using 3D Direct Energy Deposition (DED) Printing for Cementless TKA Implants: Does It Induce Chronic Inflammation?

Materials, 2020

Because of the recent technological advances, the cementless total knee arthroplasty (TKA) implan... more Because of the recent technological advances, the cementless total knee arthroplasty (TKA) implant showed satisfactory implant survival rate. Newly developed 3D printing direct energy deposition (DED) has superior resistance to abrasion as compared to traditional methods. However, there is still concern about the mechanical stability and the risk of osteolysis by the titanium (Ti) nanoparticles. Therefore, in this work, we investigated whether DED Ti-coated cobalt-chrome (CoCr) alloys induce chronic inflammation reactions through in vitro and in vivo models. We studied three types of implant surfaces (smooth, sand-blasted, and DED Ti-coated) to compare their inflammatory reaction. We conducted the in vitro effect of specimens using the cell counting kit-8 (CCK-8) assay and an inflammatory cytokine assay. Subsequently, in vivo analysis of the immune profiling, cytokine assay, and histomorphometric evaluation using C57BL/6 mice were performed. There were no significant differences in ...

Research paper thumbnail of Corrigendum: Circulating Aneuploid Cells Detected in the Blood of Patients with Infectious Lung Diseases

The Korean Journal of Thoracic and Cardiovascular Surgery, 2017

Research paper thumbnail of Detection of circulating tumor cells in patients with non-small cell lung cancer using a size-based platform

Oncology letters, 2017

The detection of circulating tumor cells (CTCs) is limited by the rarity of these cells in the pe... more The detection of circulating tumor cells (CTCs) is limited by the rarity of these cells in the peripheral blood of patients with cancer. Understanding tumor biology may be useful in the development of novel therapeutic strategies for patients with lung cancer. The present study evaluated a novel size-based filtration platform for enriching CTCs from patients with lung cancer. Blood samples were obtained from 82 patients with lung cancer for CTC analysis. CTC enrichment by size-based filtration was performed on 5-ml blood samples. The collected cells were detected by immunofluorescence using monoclonal anti-human antibodies against protein tyrosine phosphatase, receptor type C (CD45) and epithelial cell adhesion molecule (EpCAM; an epithelial cell marker), as well as a DAPI nucleic acid stain. CTCs were detected in 57 patients (69.5%) using the size-based filtration platform. The mean CTC counts, defined as the number of cells with DAPI-positive, CD45-negative and EpCAM-positive stai...

Research paper thumbnail of Circulating Aneuploid Cells Detected in the Blood of Patients with Infectious Lung Diseases

The Korean journal of thoracic and cardiovascular surgery, 2017

The identification of circulating tumor cells (CTCs) is clinically important for diagnosing cance... more The identification of circulating tumor cells (CTCs) is clinically important for diagnosing cancer. We have previously developed a size-based filtration platform followed by epithelial cell adhesion molecule immunofluorescence staining for detecting CTCs. To characterize CTCs independently of cell surface protein expression, we incorporated a chromosomal fluorescence in situ hybridization (FISH) assay to detect abnormal copy numbers of chromosomes in cells collected from peripheral blood samples by the size-based filtration platform. Aneuploid cells were detected in the peripheral blood of patients with lung cancer. Unexpectedly, aneuploid cells were also detected in the control group, which consisted of peripheral blood samples from patients with benign lung diseases, such as empyema necessitatis and non-tuberculous mycobacterial lung disease. These findings suggest that chromosomal abnormalities are observed not only in tumor cells, but also in benign infectious diseases. Thus, ou...

Research paper thumbnail of Investigation of influence of Proteus mirabilis LPS polysaccharide part on the murine immune cells activation

Archivum immunologiae et therapiae experimentalis, 1999

The biological activities were investigated of Proteus mirabilis lipopolysaccharides (LPSs) and t... more The biological activities were investigated of Proteus mirabilis lipopolysaccharides (LPSs) and their fragments, namely, the induction of nitric oxide (NO) and interleukin 1 (IL-1) synthesis by murine macrophages and the proliferation of murine spleen cells. The O-specific polysaccharide (F1), core oligosaccharide (F2) and lipid A were as effective as intact LPS in stimulating murine macrophages to produce NO. IL-1 synthesis was also induced by all studied types of endotoxins (S, Ra, Re) and partial structures, however F1, F2 and lipid A fractions required the presence of serum. In contrast to LPS, the O-specific polysaccharide, core oligosaccharide and lipid A were not able to induce the blast response of murine non-adherent splenocytes.

Research paper thumbnail of Effect of donor age on the proportion of mesenchymal stem cells derived from anterior cruciate ligaments

PloS one, 2015

The characteristics of anterior cruciate ligament (ACL)-derived mesenchymal stem cells (MSCs), su... more The characteristics of anterior cruciate ligament (ACL)-derived mesenchymal stem cells (MSCs), such as proportion and multilineage potential, can be affected by donor age. However, the qualitative and quantitative features of ACL MSCs isolated from younger and older individuals have not yet been compared directly. This study assessed the phenotypic and functional differences in ACL-MSCs isolated from younger and older donors and evaluated the correlation between ACL-MSC proportion and donor age. Torn ACL remnants were harvested from 36 patients undergoing ACL reconstruction (young: 29.67 ± 10.92 years) and 33 undergoing TKA (old: 67.96 ± 5.22 years) and the proportion of their MSCs were measured. The mean proportion of MSCs was slightly higher in older ACL samples of the TKA group than of the younger ACL reconstruction group (19.69 ± 8.57% vs. 15.33 ± 7.49%, p = 0.024), but the proportions of MSCs at passages 1 and 2 were similar. MSCs from both groups possessed comparable multiline...

Research paper thumbnail of Ethanol-dispersed polymer nanofiber net for highly-selective capture of lymph node CD4+ T cells

Research paper thumbnail of Synovial fluid CD34− CD44+ CD90+ mesenchymal stem cell levels are associated with the severity of primary knee osteoarthritis

Osteoarthritis and Cartilage, 2012

Research paper thumbnail of Augmentation of natural cytotoxicity by chronic low-dose ionizing radiation in murine natural killer cells primed by IL-2

Journal of Radiation Research, 2012

The possible beneficial effects of chronic low-dose irradiation (LDR) and its mechanism of action... more The possible beneficial effects of chronic low-dose irradiation (LDR) and its mechanism of action in a variety of pathophysiological processes such as cancer are a subject of intense investigation. While animal studies involving long-term exposure to LDR have yielded encouraging results, the influence of LDR at the cellular level has been less well defined. We reasoned that since natural killer (NK) cells constitute an early responder to exogenous stress, NK cells may reveal sentinel alterations in function upon exposure to LDR. When purified NK cells received LDR at 4.2 mGy/h for a total of 0.2 Gy in vitro, no significant difference in cell viability was observed. Likewise, no functional changes were detected in LDR-exposed NK cells, demonstrating that LDR alone was insufficient to generate changes at the cellular level. Nonetheless, significant augmentation of cytotoxic, but not proliferative, function was detected when NK cells were stimulated with low-dose IL-2 prior to irradiation. This enhancement of NK cytotoxicity was not due to alterations in NK-activating receptors, NK1.1, NKG2D, CD69 and 2B4, or changes in the rate of early or late apoptosis. Therefore, LDR, in the presence of suboptimal cytokine levels, can facilitate anti-tumor cytotoxicity of NK cells without influencing cellular proliferation or apoptosis. Whether these results translate to in vivo consequences remains to be seen; however, our data provide initial evidence that exposure to LDR can lead to subtle immune-enhancing effects on NK cells and may explain, in part, the functional basis underlying, diverse beneficial effects seen in the animals chronically exposed to LDR.

Research paper thumbnail of Clusterin synergizes with IL-2 for the expansion and IFN-  production of natural killer cells

Journal of Leukocyte Biology, 2010

CLU is a secreted, multifunctional protein implicated in several immunologic and pathologic condi... more CLU is a secreted, multifunctional protein implicated in several immunologic and pathologic conditions. As the level of serum CLU was shown to be elevated during inflammatory responses, we questioned if CLU might interact with circulating lymphocytes leading to functional consequences. To assess this possibility directly, mouse splenocytes and purified NK cells were cultured with varying dose of CLU, and its effect on cell proliferation was examined. Our data showed that CLU up-regulated DNA synthesis and expansion of NK cells significantly in response to a suboptimal, but not maximal, dose of IL-2, and CLU alone did not exhibit such effects. This CLU-mediated synergy required the co-presence of CLU at the onset of IL-2 stimulation and needed a continuous presence during the rest of the culture. Importantly, NK cells stimulated with CLU showed increased formation of cell clusters and a CD69 activation receptor, representing a higher cellular activation status compared with those from the control group. Furthermore, these NK cells displayed elevated IFN-γ production upon RMA/S tumor target exposures, implying that CLU regulates not only NK cell expansion but also effector function of NK cells. Collectively, our data present a previously unrecognized function of CLU as a novel regulator of NK cells via providing costimulation required for cell proliferation and IFN-γ secretion. Therefore, the role of CLU on NK cells should be taken into consideration for the previously observed, diverse functions of CLU in chronic inflammatory and autoimmune conditions.

Research paper thumbnail of Korean red ginseng (Panax ginseng) ameliorates type 1 diabetes and restores immune cell compartments

Journal of Ethnopharmacology, 2012

Ethnopharmacological relevance: Historical records reveal that in traditional medicine, a disease... more Ethnopharmacological relevance: Historical records reveal that in traditional medicine, a disease similar to diabetes was treated with ginseng. Korean red ginseng has been considered beneficial as a dietary supplement for its anti-diabetic potential. Aim: This study was designed to investigate the prophylactic potential of Korean red ginseng (KRG) extract (Panax ginseng C.A. Meyer Radix Rubra) in a well-established mouse model of Type 1 diabetes (T1D). Materials and methods: The prophylactic effect of KRG extract was evaluated in mice fed with KRG extract for two weeks prior to induction of diabetes by streptozotocin (STZ) administration. Glucose levels and glucose challenge test results of KRG-treated diabetic mice were compared to those of untreated diabetic mice and healthy control mice. Examination of the immune compartments in lymphoid organs and immunohistochemical staining of pancreas for islet cell morphology and insulin producing beta cells were performed. Results: KRG extract significantly lowered blood glucose levels to an average of 250 mg/dl from 350 mg/dl and improved glucose challenge testing when applied as prophylaxis. Histological findings indicated that KRG extract protected against STZ-induced destruction of pancreatic tissue and restored insulin secretion. Strikingly, this effect was accompanied by restoration of lymphocytes in secondary lymphoid organs, suggesting that KRG extract facilitated immune homeostasis. Conclusion: This is the first report to demonstrate the prophylactic function of KRG extract in ameliorating the hyperglycemia of T1D. Immune compartments of diabetic mice were found to be preserved in KRG-treated mice suggesting that Korean red ginseng may benefit T1D patients, not only for its hypoglycemic but also for its immunomodulatory effects.

Research paper thumbnail of Tumor cells expressing membrane-bound form of IL-4 induce antitumor immunity

Gene Therapy, 2000

Local cytokine concentrations are required for inhibition of tumor growth with less toxic side-ef... more Local cytokine concentrations are required for inhibition of tumor growth with less toxic side-effects. However, genetically engineered tumor cells secreting cytokines still induce toxicity and activate bystander cells. To circumvent such problems, membrane-bound forms of IL-4 (IL-4m) were expressed on MethA fibrosarcoma tumor cells. Chimeric forms of IL-4 with the type I transmembrane protein CD4 or type II transmembrane protein TNF were designed to express IL-4 in opposite orientations on the tumor cell surface. The IL-4m on tumor clones was able to support cell growth of the IL-4 dependent cytotoxic cell line (CT.4S) and

Research paper thumbnail of Erratum: Oncolytic adenovirus co-expressing IL-12 and IL-18 improves tumor-specific immunity via differentiation of T cells expressing IL-12Rβ2 or IL-18Rα

Research paper thumbnail of Impact of chronicity of injury on the proportion of mesenchymal stromal cells derived from anterior cruciate ligaments

Cytotherapy, 2014

Background aims. The graft-healing potential of mesenchymal stromal cells (MSCs) derived from the... more Background aims. The graft-healing potential of mesenchymal stromal cells (MSCs) derived from the remnants of ruptured anterior cruciate ligaments (ACLs) after ACL reconstruction may depend on the chronicity of the injury. The aim of this study was to assess the quantitative and phenotypic differences between MSCs isolated from ACL remnants in patients with (sub) acute and chronic tearing. Methods. Torn ACL remnants were harvested during ACL reconstruction from 41 patients, 24 with (sub)acute ACL (<6 months from injury to surgery) and 17 with chronic ACL (time interval >6 months) tears. MSCs isolated from these samples were assessed for quantitative and phenotypic differences, and the correlation between the proportion of MSCs and the chronicity of ACL tear was evaluated. Results. At passage 0, the mean proportion of MSCs (CD34 À , CD44 þ , CD90 þ and CD105 þ) was higher in (sub)acute than in chronic ACL tear samples (20.69% AE 7.82% versus 9.85% AE 8.01%, P < 0.001). At passages 1 and 2, however, MSC proportions did not differ significantly in the two groups. Time interval showed a negative correlation with MSC proportion only at passage 0 (r ¼ À0.505, P < 0.001). The optimal cutoff value for time from injury to surgery yielding <10% freshly isolated ACL-MSCs, a percentage expected to have low tissue healing potential, was 23.5 months. Conclusions. The proportion of freshly isolated MSCs was higher in samples from patients with (sub)acute tearing than in chronic ACL tearing and negatively correlated with the time interval between trauma and surgery.

Research paper thumbnail of Isolation and expansion of synovial CD34−CD44+CD90+mesenchymal stem cells: comparison of an enzymatic method and a direct explant technique

Connective Tissue Research, 2010

Synovium-derived mesenchymal stem cells (MSCs) offer a promising therapeutic option for cartilage... more Synovium-derived mesenchymal stem cells (MSCs) offer a promising therapeutic option for cartilage regeneration. The conventional method of MSC isolation involves single-cell suspensions using collagenases. Recently, a nonenzymatic explant technique was developed to isolate MSCs. We compared these techniques in the isolation of functional MSCs. MSCs were isolated from human fibrous and adipose synovium of osteoarthritic patients using explants or enzymatic methods. Total cell number, percentage of MSCs, and surface marker expression of MSCs were measured following expansion. Multipotentiality was determined using a MSC functional identification kit. MSCs isolated from fibrous or adipose synovium using these two techniques expressed similar levels of the surface markers CD44, CD90, and CD105, and displayed similar multipotentiality in generating adipocytes, osteoblasts, and chondrocytes. Total cell number and number of CD34(-)CD44(+)CD90(+) MSCs after 10-day expansion were similar in each culture, regardless of the source and method used, although the percentage of MSCs was slightly higher in explant cultures. There were no correlations between MSC yield and patient age, Hospital for Special Surgery score, and degree of deformity under all culture conditions. Both the enzymatic and explant techniques yielded similar yields of MSCs with similar characteristics. Because the explant technique is simpler and less invasive, it may be preferred over enzymatic techniques for isolating MSCs from the synovium of osteoarthritic patients for cartilage regeneration.

Research paper thumbnail of API5 Confers Tumoral Immune Escape through FGF2-Dependent Cell Survival Pathway

Cancer Research, 2014

Identifying immune escape mechanisms used by tumors may define strategies to sensitize them to im... more Identifying immune escape mechanisms used by tumors may define strategies to sensitize them to immunotherapies to which they are otherwise resistant. In this study, we show that the antiapoptotic gene API5 acts as an immune escape gene in tumors by rendering them resistant to apoptosis triggered by tumor antigen-specific T cells. Its RNAi-mediated silencing in tumor cells expressing high levels of API5 restored antigen-specific immune sensitivity. Conversely, introducing API5 into API5low cells conferred immune resistance. Mechanistic investigations revealed that API5 mediated resistance by upregulating FGF2 signaling through a FGFR1/PKCδ/ERK effector pathway that triggered degradation of the proapoptotic molecule BIM. Blockade of FGF2, PKCδ, or ERK phenocopied the effect of API5 silencing in tumor cells expressing high levels of API5 to either murine or human antigen-specific T cells. Our results identify a novel mechanism of immune escape that can be inhibited to potentiate the ef...