Jung Seung Lee

Polydopamine-mediated surface modification of scaffold materials for human neural stem cell engineering

Surface modification of tissue engineering scaffolds and substrates is required for improving the efficacy of stem cell therapy by generating physicochemical stimulation promoting proliferation and differentiation of stem cells. However, typical surface modification methods including chemical conjugation or physical absorption have several limitations such as multistep, complicated procedures, surface denaturation, batch-to-batch inconsistencies, and low surface conjugation efficiency. In this study, we report a mussel-inspired, biomimetic approach to surface modification for efficient and reliable manipulation of human neural stem cell (NSC) differentiation and proliferation. Our study demonstrates that polydopamine coating facilitates highly efficient, simple immobilization of neurotrophic growth factors and adhesion peptides onto polymer substrates. The growth factor or peptide-immobilized substrates greatly enhance differentiation and proliferation of human NSCs (human fetal brain-derived NSCs and human induced pluripotent stem cell-derived NSCs) at a level comparable or greater than currently available animal-derived coating materials (Matrigel) with safety issues. Therefore, polydopamine-mediated surface modification can provide a versatile platform technology for developing chemically defined, safe, functional substrates and scaffolds for therapeutic applications of human NSCs.

Androgen receptor expression is significantly associated with better outcomes in estrogen receptor-positive breast cancers

BACKGROUND The objective of the study was to evaluate the implications of androgen receptor (AR) in breast cancers. PATIENTS AND METHODS We investigated immunohistochemical AR expression from the tissue microarrays of 931 patients between 1999 and 2005, and analyzed demographics and outcomes using uni-/multivariate analyses. Tumors with ≥10% nuclear-stained cells were considered positive for AR. RESULTS AR was expressed in 58.1% of patients. AR was significantly related to older age at diagnosis, smaller size, well-differentiated tumors, higher positivity of hormone receptors, non-triple-negative breast cancers (non-TNBCs), and lower proliferative index. In estrogen receptor (ER)-negative tumors, AR was distinctively associated with human epidermal growth factor receptor type 2 (HER2) overexpression. With a mean follow-up of 72.7 months, AR was positively related to survival in ER-positive but not in ER-negative tumors. In Coxs models, AR was an independent prognostic factor for disease-free survival in ER-positive cancers. Interestingly, molecular apocrine tumors (ER negative and AR positive) with HER2 positive status showed trends of poorer outcome, but AR had no impact on survival in patients with TNBC. CONCLUSIONS AR is significantly associated with favorable features in breast cancers and related to better outcomes in ER-positive not in ER-negative tumors. These results suggest that AR could be an additional marker for endocrine responsiveness in ER-positive cancers and a candidate for therapeutic targeting of ER-negative tumors.

Bioinspired, Calcium-Free Alginate Hydrogels with Tunable Physical and Mechanical Properties and Improved Biocompatibility

Alginate hydrogels are for various biomedical applications including tissue engineering, cell therapy, and drug delivery. However, it is not easy to control swelling or viscoelastic and biophysical properties of alginate hydrogels prepared by conventional cross-linking methods (ionic interaction using divalent cations). In this study, we describe a bioinspired approach for preparing divalent ion-free alginate hydrogels that exhibit tunable physical and mechanical properties and improved biocompatibility due to the absence of cations in the gel matrices. We conjugated dopamine, a minimalized adhesive motif found in the holdfast pads of mussels, to alginate backbones (alginate-catechol) and the tethered catechols underwent oxidative cross-linking. This resulted in divalent cation-free alginate hydrogels. The swelling ratios and moduli of the alginate-catechol hydrogels are readily tunable, which is difficult to achieve in ionic bond-based alginate hydrogels. Furthermore, alginate-catechol hydrogels enhanced the survival of various human primary cells including stem cells in the three-dimensional gel matrix, indicating that intrinsic cytotoxicity caused by divalent cations becomes negligible when employing catechol oxidation for alginate cross-linking. The inflammatory response in vivo was also significantly attenuated compared to conventional alginate hydrogels with calcium cross-linking. This biomimetic approach for the preparation of alginate hydrogels may provide a novel platform technology to develop tunable, functional, biocompatible, three-dimensional scaffolds for tissue engineering and cell therapy.

Liver Extracellular Matrix Providing Dual Functions of Two-Dimensional Substrate Coating and Three-Dimensional Injectable Hydrogel Platform for Liver Tissue Engineering

Decellularization of tissues or organs can provide an efficient strategy for preparing functional scaffolds for tissue engineering. Microstructures of native extracellular matrices and their biochemical compositions can be retained in the decellularized matrices, providing tissue-specific microenvironments for efficient tissue regeneration. Here, we report the versatility of liver extracellular matrix (LEM) that can be used for two-dimensional (2D) coating and three-dimensional (3D) hydrogel platforms for culture and transplantation of primary hepatocytes. Collagen type I (Col I) has typically been used for hepatocyte culture and transplantation. In this study, LEM was compared with Col I in terms of biophysical and mechanical characteristics and biological performance for enhancing cell viability, differentiation, and hepatic functions. Surface properties of LEM coating and mechanical properties and gelation kinetics of LEM hydrogel could be manipulated by adjusting the LEM concentration. In addition, LEM hydrogel exhibited improved elastic properties, rapid gelation, and volume maintenance compared to Col I hydrogel. LEM coating significantly improved hepatocyte functions such as albumin secretion and urea synthesis. More interestingly, LEM coating upregulated hepatic gene expression of human adipose-derived stem cells, indicating enhanced hepatic differentiation of these stem cells. The viability and hepatic functions of primary hepatocytes were also significantly improved in LEM hydrogel compared to Col I hydrogel both in vitro and in vivo. Albumin and hepatocyte transcription factor expression was upregulated in hepatocytes transplanted in LEM hydrogels. In conclusion, LEM can provide functional biomaterial platforms for diverse applications in liver tissue engineering by promoting survival and maturation of hepatocytes and hepatic commitment of stem cells. This study demonstrates the feasibility of decellularized matrix for both 2D coating and 3D hydrogel in liver tissue engineering.

Predictive factors for nephritis, relapse, and significant proteinuria in childhood Henoch-Schonlein purpura

Objective: To identify predictive factors for nephritis, relapse, and significant proteinuria in childhood Henoch–Schönlein purpura (HSP). Methods: Two hundred and six consecutive patients with HSP (93 female, 113 male), followed up at a single centre between 1996 and 2001, were analysed retrospectively. They were regularly monitored for clinical and laboratory parameters for renal sequelae and relapse. Results: Nephritis was seen in 78 patients (38%), relapse in 52 (25%), and significant proteinuria in 39 (19%). In univariate analysis, an older age at onset (>10 years), persistent purpura, severe bowel angina, and relapse were identified as factors associated with nephritis and significant proteinuria. Relapse‐related factors were an older age, persistent purpura, severe bowel angina, and leucocytosis. Logistic regression analysis showed that nephritis was significantly associated with an older age, persistent purpura, and relapse, and significant proteinuria was closely related to severe bowel angina and relapse. Conclusion: We identified some predictors for nephritis, relapse, and significant proteinuria in childhood HSP, and close attention should be paid to those patients with the risk factors, such as an older age at onset, persistent purpura, severe bowel angina, and relapse.

Hybrid natural orifice transluminal endoscopic surgery: endoscopic full-thickness resection of early gastric cancer and laparoscopic regional lymph node dissection--14 human cases.

BACKGROUND AND STUDY AIM Minimally invasive treatment has become a mainstay management strategy for early gastric cancer (EGC). Full-thickness incision of the gastric wall using natural orifice transluminal endoscopic surgery (NOTES) has been reported but is not easily applicable in clinical settings at present. The aim of the current study was to assess the feasibility of hybrid NOTES, which consists of endoscopic full-thickness gastric resection and a laparoscopic lymphadenectomy. PATIENTS AND METHODS This was a prospective, pilot study at a single tertiary care referral center. A total of 14 patients with EGC located above the lower third of the stomach underwent hybrid NOTES. Clinically, the patients had contraindications to exclusive treatment using endoscopic submucosal dissection (ESD). The main outcome measure was technical success of hybrid NOTES. RESULTS All cases were resected en bloc with negative surgical margins. Histologically, four cases were mucosal cancers, and 10 cases were submucosal cancers. The median tumor size was 26 mm (range 12 - 90 mm). Lymphatic vessel invasion was found in four cases without lymph node metastasis (LNM). The median number of obtained lymph nodes was 18 (range 7 - 67). LNM was discovered in one case of undifferentiated submucosal cancer without lymphovascular invasion. Hybrid NOTES was conducted without intraoperative or postoperative adverse events in nine cases. The median operating time and estimated blood loss of successful cases were 143 minutes (range 110 - 253 minutes) and 16 mL (range 5 - 30 mL), respectively. The median hospital stay was 6 days (range 4 - 10 days). Five cases were converted to a subtotal gastrectomy for various reasons. CONCLUSIONS Hybrid NOTES could be a bridge between endoscopic resection and laparoscopic surgery and may prevent extensive gastrectomy in patients with EGC.

Combination treatment by 10 600 nm ablative fractional carbon dioxide laser and narrowband ultraviolet B in refractory nonsegmental vitiligo: a prospective, randomized half-body comparative study

Background  Vitiligo is a common acquired depigmentation disorder caused by the loss of melanocytes. Despite the numerous treatment modalities available for vitiligo, responses to treatment are still unsatisfactory. For this reason, new treatment modalities and approaches are needed.

Effect of drug-eluting metal stents in benign esophageal stricture: an in vivo animal study.

BACKGROUND AND STUDY AIMS The aim of this study in canines was to investigate the effectiveness and safety of self-expandable metal stents, which were coated with paclitaxel to minimize the tissue response. MATERIALS AND METHODS 14 dogs (5-10 kg) were randomly allocated to two groups. Drug-eluting stents (DES, n = 7) or nondrug-eluting stents (non-DES, n = 7) were endoscopically inserted and fixed in the esophagus of healthy dogs. Every 2 weeks, for a maximum period of 8 weeks, an endoscopic examination was performed to evaluate the status of stent insertion, the grade of tissue hyperplasia, and mucosal change at both ends of the stent. RESULTS One case of stent migration was observed after 4 weeks in the non-DES group. In this group, tissue reaction and hyperplasia remained for more than 4 weeks after stent insertion. By contrast, an endoscopic examination of the surrounding esophageal mucosa in the DES group showed very little tissue reaction, and the stent was easily separated from the esophageal tissue. CONCLUSION Although further studies are required to confirm our results, we suggest that these newly designed DES may provide an alternative tool to manage refractory benign esophageal stricture.

Three-dimensional extracellular matrix-mediated neural stem cell differentiation in a microfluidic device

Here, we report a unique method to quantify the effects of in vivo-like extracellular matrix (ECM) for guiding differentiation of neural stem cells (NSCs) in three-dimensional (3D) microenvironments using quantitative real-time polymerase chain reaction (qRT-PCR). We successfully monitored and quantified differentiation of NSCs in small volume ECMs and found that differentiation of NSCs, especially those differentiating towards neuronal and oligodendrocytic lineages, is significantly enhanced by 3D microenvironments reconstituted in the microfluidic channels.

Switchable Water‐Adhesive, Superhydrophobic Palladium‐Layered Silicon Nanowires Potentiate the Angiogenic Efficacy of Human Stem Cell Spheroids

A switchable water-adhesive, super-hydrophobic nanowire surface is developed for the formation of functional stem cell spheroids. The sizes of hADSC spheroids are readily controllable on the surface. Our surface increases cell-cell and cell-matrix interaction, which improves viability and paracrine secretion of the spheroids. Accordingly, the hADSC spheroids produced on the surface exhibit significantly enhanced angiogenic efficacy.