The transdifferentiation of human dedifferentiated fat cells into fibroblasts: An in vitro experimental pilot study.

BACKGROUND: Skin grafting is a common method of treating damaged skin; however, surgical complications may arise in patients with poor health. Currently, no effective conservative treatment is available for extensive skin loss. Mature adipocytes, which constitute a substantial portion of adipose tissue, have recently emerged as a potential source of stemness. When de-lipidated, these cells exhibit fibroblast-like characteristics and the ability to redifferentiate, offering homogeneity and research utility as "dedifferentiated fat cells." METHODS AND RESULTS: We conducted an in vitro study to induce fibroblast-like traits in the adipose tissue by transdifferentiating mature adipocytes for skin regeneration. Human subcutaneous fat tissues were isolated and purified from mature adipocytes that underwent a transformation process over 14 days of cultivation. Microscopic analysis revealed lipid degradation over time, ultimately transforming cells into fibroblast-like forms. Flow cytometry was used to verify their characteristics, highlighting markers such as CD90 and CD105 (mesenchymal stem cell markers) and CD56 and CD106 (for detecting fibroblast characteristics). Administering dedifferentiated fat cells with transforming growth factor-ß at the identified optimal differentiation concentration of 5 ng/mL for a span of 14 days led to heightened expression of alpha smooth muscle actin and fibronectin, as evidenced by RNA and protein analysis. Meanwhile, functional validation through cell sorting demonstrated limited fibroblast marker expression in both treated and untreated cells after transdifferentiation by transforming growth factor-ß. CONCLUSION: Although challenges remain in achieving more effective transformation and definitive fibroblast differentiation, our trial could pave the way for a novel skin regeneration treatment strategy.

Targeting Nuclear Mechanics Mitigates the Fibroblast Invasiveness in Pathological Dermal Scars Induced by Matrix Stiffening.

Pathological dermal scars such as keloids present significant clinical challenges lacking effective treatment options. Given the distinctive feature of highly stiffened scar tissues, deciphering how matrix mechanics regulate pathological progression can inform new therapeutic strategies. Here, it is shown that pathological dermal scar keloid fibroblasts display unique metamorphoses to stiffened matrix. Compared to normal fibroblasts, keloid fibroblasts show high sensitivity to stiffness rather than biochemical stimulation, activating cytoskeletal-to-nuclear mechanosensing molecules. Notably, keloid fibroblasts on stiff matrices exhibit nuclear softening, concomitant with reduced lamin A/C expression, and disrupted anchoring of lamina-associated chromatin. This nuclear softening, combined with weak adhesion and high contractility, facilitates the invasive migration of keloid fibroblasts through confining matrices. Inhibiting lamin A/C-driven nuclear softening, via lamin A/C overexpression or actin disruption, mitigates such invasiveness of keloid fibroblasts. These findings highlight the significance of the nuclear mechanics of keloid fibroblasts in scar pathogenesis and propose lamin A/C as a potential therapeutic target for managing pathological scars.

Design of a Bioinspired Robust Three-Dimensional Cross-Linked Polymer Binder for High-Performance Li-Ion Battery Applications.

Si has the highest theoretical capacity (4200 mA h g-1) among conventional anode materials, such as graphite (372 mA h g-1), but its large volume expansion leads to deterioration of the battery performance. To overcome this problem (issue), we investigated the use of polysaccharide-based 3D cross-linked network binders for Si anodes, in which the polysaccharide formed an effective 3D cross-linked network around Si particles via cross-linking of polysaccharide with citric acid (CA). Sodium alginate (SA), a natural polysaccharide extracted from brown algae, is a suitable binder material for Si anodes because its abundant hydroxyl (-OH) and carboxyl (-COOH) groups form hydrogen and covalent bonds with the -OH groups present on the Si surface. We found that CA-cross-linked (CA-SA) could effectively prevent the volume expansion of Si anodes through the formation of 3D cross-linked network structures. In addition, the CA-SA binders provide enhanced adhesion strength, enabling the fabrication of more robust electrodes than those prepared using binders with linear structures ("linear binders"). In particular, the fabricated Si-based electrode (high mass loading of 1.5 mg cm-2) with CA-SA binder exhibited outstanding areal capacity (∼2.7 mA h cm-2) and excellent cycle retention (∼100% after 100 cycles).

The Health Status and Management of Migrant Workers in Cheonan: A Comparison Study With Korean Citizens.

Migrant workers face challenging working conditions, resulting in physical and mental vulnerability. The objective is to identify their health vulnerabilities and ensure their right to health. Health records of 163 migrant workers (113 males and 50 females) (Group A) and 163 Korean citizens (Group B) visiting our institution were analyzed from August 2021 to July 2022. Both groups underwent urine analysis, chest radiography, and various blood tests. Statistical analysis using independent t-tests and χ² tests was performed. Group A had a significantly higher rate of hepatitis B virus surface antigen-positive patients, lower vaccination rates for hepatitis B, and poorer nutritional status compared to Group B. Group B generally exhibited higher levels of albumin, glucose, total cholesterol, and thyroid-stimulating hormone. There were significant quantitative differences in multiple blood cell and hemoglobin measurements between the two groups. These findings emphasize the need for policy support and public awareness to protect the health rights of migrant workers.

Human Fibroblast Growth Factor-Treated Adipose-Derived Stem Cells Facilitate Wound Healing and Revascularization in Rats with Streptozotocin-Induced Diabetes Mellitus.

Diabetes mellitus contributes to 15-25% of all chronic foot ulcers. Peripheral vascular disease is a cause of ischemic ulcers and exacerbates diabetic foot disease. Cell-based therapies are viable options to restore damaged vessels and induce the formation of new vessels. Adipose-derived stem cells (ADSCs) have the potential for angiogenesis and regeneration because of their greater paracrine effect. Preclinical studies are currently using other forced enhancement techniques (e.g., genetic modification or biomaterials) to increase the efficacy of human ADSC (hADSC) autotransplantation. Unlike genetic modifications and biomaterials, many growth factors have been approved by the equivalent regulatory authorities. This study confirmed the effect of enhanced human ADSC (ehADSC)s with a cocktail of FGF and other pharmacological agents to promote wound healing in diabetic foot disease. In vitro, ehADSCs exhibited a long and slender spindle-shaped morphology and showed significantly increased proliferation. In addition, it was shown that ehADSCs have more functionalities in oxidative stress toleration, stem cell stemness, and mobility. In vivo, the local transplantation of 1.2 × 106 hADSCs or ehADSCs was performed in animals with diabetes induced by STZ. The ehADSC group showed a statistically decreased wound size and increased blood flow compared with the hADSC group and the sham group. Human Nucleus Antigen (HNA) positive cells were observed in some ADSC-transplanted animals. The ehADSC group showed a relatively higher portion of HNA-positive animals than the hADSC group. The blood glucose levels showed no significant difference among the groups. In conclusion, the ehADSCs showed a better performance in vitro, compared with conventional hADSCs. Additionally, a topical injection of ehADSCs into diabetic wounds enhanced wound healing and blood flow, while improving histological markers suggesting revascularization.

The use of machine learning for investigating the role of plastic surgeons in anatomical injuries: A retrospective observational study.

While plastic surgeons have been historically indispensable in the reconstruction of posttraumatic defects, their role in trauma centers worldwide has not been clearly defined. Therefore, we aimed to investigate the contribution of plastic surgeons in trauma care using machine learning from an anatomic injury viewpoint. We conducted a retrospective study reviewing the data for all trauma patients of our hospital from March 2019 to February 2021. In total, 4809 patients were classified in duplicate according to the 17 trauma-related departments while conducting the initial treatment. We evaluated several covariates, including age, sex, cause of trauma, treatment outcomes, surgical data, and severity indices, such as the Injury Severity Score and Abbreviated Injury Scale (AIS). A random forest algorithm was used to rank the relevance of 17 trauma-related departments in each category for the AIS and outcomes. Additionally, t test and chi-square test were performed to compare two groups, which were based on whether the patients had received initial treatment in the trauma bay from the plastic surgery department (PS group) or not (non-PS group), in each AIS category. The department of PS was ranked first in the face and external categories after analyzing the relevance of the 17 trauma-related departments in six categories of AIS, through the random forest algorithm. Of the 1108 patients in the face category of AIS, the PS group was not correlated with all outcomes, except for the rate of discharge to home (P < .0001). Upon re-verifying the results using random forest, we found that PS did not affect the outcomes. In the external category in AIS, there were 30 patients in the PS group and 56 patients in the non-PS group, and there was no statistically significant difference between the two groups when comparing the outcomes. PS has contributed considerably to the face and external regions among the six AIS categories; however, there was no correlation between plastic surgical treatment and the outcome of trauma patients. We investigated the plastic surgeons' role based on anatomical injury, using machine learning for the first time in the field of trauma care.

A quantitative analysis of trauma patients having undergone plastic surgery.

PURPOSE: While plastic surgeons have been historically indispensable in reconstruction of posttraumatic defects, their role in Level I trauma centers around the world has not yet been clearly approved. This study aims to assess the contribution of plastic surgeons in major trauma care by evaluating the characteristics of trauma patients underwent plastic surgery at a Level I trauma center. METHOD: From November 2014 to October 2020, we conducted a retrospective review of our hospital's Trauma Registry System for patients with an Injury Severity Score (ISS) of 9 or higher. Of all of 7174 patients, the plastic surgery (PS) department treated 870 patients; the 6304 patients not treated by the PS were classified as the Non-PS. Then, we performed propensity score matching to reduce the statistical bias, after the death in the emergency room and the missing value were considered exclusion criteria. RESULT: The mean ISS showed no significant difference between two groups (16.29 ± 7.04 in the PS vs. 16.68 ± 9.16 in the Non-PS, p = 0.3221). According to investigate the Abbreviated Injury Scale, both head and neck (65.0%) and face (46.4%) categories showed significantly higher in the PS group than the Non-PS group (p < 0.0001), and its contribution ratio was 2.151 and 21.822 times, respectively. CONCLUSION: This study revealed the specialty of plastic surgery was face area in trauma care. We thus argue that plastic surgical care is imperative for trauma patients, and expect to be implicated in trauma system planning.

Midface Infection after COVID-19 Vaccination in a Patient with Calcium Hydroxylapatite Dermal Filler: A Case Report and Literature Review.

The emergence of vaccines for coronavirus disease 2019 (COVID-19) raises risk of possible adverse events from interaction between the vaccines and facial aesthetic care. A 47-year-old female with no medical comorbidities visited our emergency room due to midface painful swelling after 3 hours following receiving the second dose of the messenger RNA BNT162b2 COVID-19 vaccine. About 14 years ago, she underwent nonsurgical augmentation on the nasojugal groove with a calcium hydroxylapatite dermal filler. We performed incision and drainage under general anesthesia on the next day. During operation, yellowish pus-like materials bulged out. After an operation, we performed a combination therapy with antibiotics and methylprednisolone. Her symptoms improved day by day after surgery, and then a complete recovery was achieved at 3 weeks after the treatment. In conclusion, providers of aesthetic procedures are to be aware of the potential risks of such vaccines for patients who already had or seek to receive dermal filler injections.

Improved healing and macrophage polarization in oral ulcers treated with photobiomodulation (PBM).

OBJECTIVES: The effect of photobiomodulation (PBM) treatment on wound healing and macrophage polarization was investigated in vivo. Animal models of oral ulcers were simulated through chemically induced oral ulcers in rats. MATERIALS AND METHODS: PBM treatment using an infrared pulsed laser was used to treat oral ulcers in the animal models. Twelve Sprague-Dawley rats were randomly divided into four groups depending on set absorbed energy: Group 1 (control), Group 2 (30 J), Group 3 (60 J), and Group 4 (100 J). Laser treatment was performed every other day for 8 days after ulcer confirmation. Parameters used were as follows: wavelength 808 nm, power output 50 mW, spot size 10 mm, frequency 10 Hz, and pulse duration 1 millisecond. Ulcers were measured to determine the effect of the treatments over time. Histology, immunostaining, and real-time polymerase chain reaction analyses were performed to evaluate the effect of PBM treatment on macrophage-related (IL-6/IL-10) and wound-healing-related (TNF-α/TGF-ß/MMP-2) cytokine expression. RESULTS: Histological examinations indicate that the PBM treatment stimulated a higher level of wound recovery after 8 days of treatment at 60 J absorbed energy compared to other treatment groups. Analyses of relative gene expression of proinflammatory, anti-inflammatory, and tissue remodeling cytokines indicate that the macrophages in the tissue samples were predominantly characterized as M2 subtypes (alternatively activated), which possibly accounts for the accelerated tissue repair in the animal model of oral ulcer. CONCLUSION: This preliminary study stands as a proof of concept regarding the potential use of infrared laser PBM treatment for oral ulcers which have not been previously investigated upon. PBM treatment affects macrophage polarization and enhances wound healing. Further experimentation will be conducted to expand the understanding of how PBM treatment affects the healing mechanism of ulcers.

Association between the participation of the plastic surgery department and qualitative prognoses in severe trauma patients: A retrospective observational study.

Catastrophic incidents would necessitate the intervention of multiple specializations with plastic surgery (PS) as an indispensable area of expertise. In view of PS, prognostic assessment of trauma patients should be focused on the qualitative value rather than mortality because plastic surgeons rarely handled patients' vital signs in actual. Thus, we explored the association between the involvement of the PS department and qualitative prognoses for severe trauma patients. From November 2014 to December 2019, we enrolled total 529 trauma patients with an injury severity score (ISS) over 15 points. We set the prognostic factors that the rate of admission in intensive care unit (ICU), total or ICU duration of hospitalization, post-discharge progress and disability diagnosis which were regarded as qualitative prognoses. The analysis was performed with logistic regression analysis or regression analysis adjusted for age, sex, past medical history, cause of trauma, and frequency of operation. Among total of 529 patients, 290 patients in PS group and 239 patients in non-PS group were analyzed. In both groups, the under-65-year ages and male patients were significantly predominant. The rate of going home showed 2.082 times higher in PS group than non-PS group after adjusting for covariates, while there was no significant difference in diagnosis of disability. Meanwhile, overall prognoses were highly correlated with either higher ISS or lower Glasgow Coma Scale (GCS). In conclusion, higher severity generally affected to the severe trauma patient's prognoses, and the PS treatment only contributes to discharge disposition to home.

Orbital wall restoration with primary bone fragments in complex orbital fractures: A preliminary study.

BACKGROUND: We have reported orbital wall restoration surgery with primary orbital wall fragment in pure blowout fractures using a combination of transorbital and transnasal approach in pure blow out fractures. However, this method was thought to be difficult to use for complex orbital wall fractures, since the sharp screw tip that fixate the maxillary wall increases the risk of balloon ruptures. In this study, we reviewed 23 cases of complex orbital fractures that underwent orbital wall restoration surgery with primary orbital wall fragment and evaluated the result. METHODS: A retrospective review was conducted of 23 patients with complex orbital fracture who underwent orbital restoration surgery with primary orbital wall fragments between 2012 and 2019. The patients underwent orbital wall restoration surgery with primary orbital wall fragment with temporary balloon support. The surgical results were evaluated by the Naugle scale and a comparison of preoperative and postoperative orbital volume ratio. Complex fracture type, type of screw used for fixation and complications such as balloon rupture were also investigated. RESULTS: There were 23 patients with complex orbital fracture that used transnasal balloon technique for restoration. 17 cases had a successful outcome with no complications, three patients had postoperative balloon rupture, two patients had soft-tissue infection, and one patient had balloon malposition. CONCLUSION: The orbital wall restoration technique with temporary balloon support can produce favorable results when done correctly even in complex orbital wall fracture. Seventeen cases had favorable results, six cases had postoperative complications thus additional procedure seems necessary to complement this method.

Epidemiology of severe trauma patients treated by plastic surgeons: A 7-year study at a single regional trauma center in South Korea.

BACKGROUND: After the laws regulating emergency medicine were amended in 2012, regional trauma centers were established in South Korea. Plastic surgeons specialize in the simultaneous surgical care of patients with facial trauma, burns, and complicated wounds. The objective of this study was to evaluate the role of the plastic surgery department in treating severe trauma patients. METHODS: From January 2012 to December 2018, we enrolled 366 severe trauma patients with an Injury Severity Score (ISS) over 15 who received treatment by specialists in the plastic surgery department. Of these patients, 298 (81.4%) were male, and their mean age was 51.35 years (range, 6-91 years). The average ISS was 22.01 points (range, 16-75 points). RESULTS: The most common diagnosis was facial trauma (95.1%), and facial bone fracture (65.9%) was most common injury within this subgroup. Patients were referred to 1.8 departments on average, with the neurosurgery department accounting for a high proportion of collaborations (37.0%). The most common cause of trauma was traffic accidents (62.3%), and the average length of stay in the general ward and intensive care unit was 36.90 and 8.01 days, respectively. Most patients were discharged home (62.0%) without additional transfer or readmission. CONCLUSIONS: Through this study, we scoped out the role of the specialty of plastic surgery in the multidisciplinary team at regional trauma centers. These results may have implications for trauma system planning.

Delayed intraorbital infection after craniofacial bone surgery.

Intraorbital infection shows a low incidence, but it might cause blindness or even death. This case is unusual in that its origin from a craniofacial bone fracture prior to infection of the maxillary sinus. A 33-year-old female patient was referred for right cheek swelling. When she visited the emergency room, we removed right cheek hematoma and bacterial examination was done. In the past, she had craniofacial bone surgical history due to a traffic accident 6 years ago. Next day, the swelling had remained with proptosis and pus was recognized in the conjunctiva. We planned an emergency operation and removed the pus which was already spread inside the orbit. And the evaluation for sinusitis was consulted to the otorhinolaryngology department simultaneously. There were Prevotella oralis and methicillin-resistant Staphylococcus epidermidis bacterial infection in the intraorbital and sinus respectively. Afterwards, the vigorous dressing was done for over a month with intravenous antibiotics. Though the intraorbital infection was resolved, blindness and extraocular movement limitation were inevitable. In conclusion, close follow up of the maxillary sinus in facial bone fracture patients is important and aggressive treatment is needed when an infection is diagnosed.

Precision Analysis of Supraorbital Transcranial Exits Using Three Dimensional Multidetector Computed Tomography.

PURPOSE: Anatomical variation in supraorbital transcranial exits, which can be divided into the lateral supraorbital exit and the medial frontal exit, has been investigated in several studies during the past few decades. However, in previous studies, inconsistent criteria were used for classifying those exits. The authors analyzed variations in supraorbital transcranial exits using 3 dimensional multidetector computed tomography (3D MDCT), and present a consistent classification of the types of those exits with precise location measurements. METHODS: In 1181 patients (2362 orbits) who underwent facial 3D MDCT, the authors measured a set of qualitative and quantitative parameters. The qualitative parameters included an assessment of the location and type of the exit, and the number of accessory foramina. The quantitative parameters included various distance measurements. RESULTS: A frontal exit was present in 2071 orbits and a supraorbital exit in 953. Neither a frontal exit nor a supraorbital exit was found in 11 orbits. The most common type of frontal exit was the notch type, followed by the foramen type and none. The mean distance from the nasion to the frontal exit was 24.70 ± 3.50 mm on the right side and 23.69 ± 3.42 mm on the left side. CONCLUSION: In conclusion, various types of supraorbital transcranial exits were observed, of which the frontal notch was the most common. This is the first study to conduct a consistent analysis of a large sample of skulls to characterize the distribution of supraorbital transcranial exit types using a comprehensive and clear set of criteria.

Face Dissection as the Plastic Surgery Approach: Effective Method in Residency Training.

PURPOSE: The global trend of resident work-hour restrictions requires a more time efficient way of resident training. Among many training programs for learning the facial anatomy, the cadaver is the most similar to live patients. A cadaver should be used as efficiently as possible due to human dignity as well as the consideration of cost. The authors designed an effective cadaver dissection method in learning facial anatomy using the plastic surgery approach. METHOD: A 51-year-old male cadaver was used for dissection. The program was proceeded 6 times over 6 weeks, and 4 to 8 hours each day. We used standard surgical instruments with magnifying loupes. The results were analyzed through a numerical scale survey. RESULT: We planned to dissect the face from medial to lateral, cephalic to caudal, and superficial to deep portion. The overall knowledge and confidence level of the face were increased in all 7 participants. The mean knowledge level before and after the seminar was 3.00 and 4.03, respectively. Confidence level also increased through the seminar from 1.86 to 2.86. CONCLUSION: The authors believe this cadaver dissection program could optimize learning anatomical knowledge and improve resident's surgical confidence through a wide range of procedures.

Orbital Wall Restoring Surgery for Inferomedial Blowout Fracture.

Repairing a large inferomedial blowout fracture remains a challenge to orbital surgeon. The authors restored the fracture using combined transnasal and transorbital approaches using support of both paranasal sinuses. The authors compared surgical results of this novel method with those of the traditional procedure. Of 106 inferomedial blowout fracture patients who underwent surgical treatment between March 2007 and July 2013, 50 patients were selected in our study: 25 patients underwent the traditional procedure as controls, and the other 25 patients underwent orbital wall restoring surgery by our combined approach. Outcomes were evaluated in terms of the orbital volume ratio (OVR) and changes in Hertel scale. The OVR in the experimental group (7.19%) decreased more significantly than in the control group (2.71%) (P < 0.05). In conclusion, the orbit was restored more successfully following orbital wall restoring surgery with dual support than by using the traditional inferomedial blowout fracture procedure.

Orbital Floor Restoration Using the Transnasal Balloon Technique for Inferior Orbital Wall Fracture.

BACKGROUND: Restoring the volume of orbital fracture is a challenge to the surgeons. We combined the transnasal balloon technique and the transorbital approach during orbital floor reconstruction, and compared the outcomes of this technique with those of the conventional transorbital approach. METHODS: Patients with unilateral pure orbital floor fracture were divided according to the surgical method: the direct transconjunctival approach (group A, 20 patients, control group) or the combination approach with the transnasal balloon technique (group B, 20 patients, experimental group). The orbital volume ratio (OVR) was measured with the use of computed tomographic scans, and enophthalmos was checked with a Hertel exophthalmometer. RESULTS: The orbital volume ratios in both groups decreased after surgery: it was more effectively decreased in group B (7.88%) than that in group A (1.69%) (P < 0.05). CONCLUSIONS: A combination of transconjunctival exploration and transnasal restoration with balloon support was more effective in restoring the orbital volume than the conventional method.

Orbital wall restoring surgery in pure blowout fractures.

BACKGROUND: Restoring orbital volume in large blowout fractures is still a technically challenge to the orbital surgeon. In this study, we restored the orbital wall using the combination of transorbital and transnasal approach with additional supports from the paranasal sinuses, and we compared the surgical outcome to that of a conventional transorbital method. METHODS: A retrospective review of all patients with pure unilateral blowout fractures between March 2007 and March 2013 was conducted. 150 patients were classified into two groups according to the surgical method: conventional transorbital method (group A, 75 patients, control group), and the combination of transorbital and transnasal approach with additional supports from the paranasal sinuses (group B, 75 patients, experimental group). Each group was subdivided depending on fracture location: group I (inferior wall), group IM (inferomedial wall), and group M (medial wall). The surgical results were assessed by the Hertel scale and a comparison of preoperative and postoperative orbital volume ratio (OVR) values. RESULTS: In the volumetric analysis, the OVR decreased more by the experimental groups than each corresponding control groups (P<0.05). Upon ophthalmic examination, neither the differences among the groups in the perioperative Hertel scale nor the preoperative and postoperative Hertel scales were statistically significant (P>0.05). CONCLUSIONS: Our surgical results suggest that orbital volume was more effectively restored by the combination of transorbital and transnasal approach with additional supports from the paranasal sinuses than the conventional method, regardless of the type of fracture.

Double antiangiogenic protein, DAAP, targeting VEGF-A and angiopoietins in tumor angiogenesis, metastasis, and vascular leakage.

Two vascular growth factor families, VEGF and the angiopoietins, play critical and coordinate roles in tumor progression and metastasis. A single inhibitor targeting both VEGF and angiopoietins is not available. Here, we developed a chimeric decoy receptor, namely double anti-angiogenic protein (DAAP), which can simultaneously bind VEGF-A and angiopoietins, blocking their actions. Compared to VEGF-Trap or Tie2-Fc, which block either VEGF-A or angiopoietins alone, we believe DAAP is a highly effective molecule for regressing tumor angiogenesis and metastasis in implanted and spontaneous solid tumors; it can also effectively reduce ascites formation and vascular leakage in an ovarian carcinoma model. Thus, simultaneous blockade of VEGF-A and angiopoietins with DAAP is an effective therapeutic strategy for blocking tumor angiogenesis, metastasis, and vascular leakage.

L1 cell adhesion molecule is a novel therapeutic target in intrahepatic cholangiocarcinoma.

PURPOSE: Intrahepatic cholangiocarcinoma (ICC), a highly malignant hepatobiliary cancer, has a poor prognosis and is refractory to conventional therapies. The aim of this study is to discover a novel molecular target for the treatment of ICC. EXPERIMENTAL DESIGN: To discover novel cancer-associated membrane antigens expressed in ICC cells, we generated monoclonal antibodies (mAb) by immunizing mice with intact ICC cell lines and screened for those that bind to the plasma membrane of ICC cells but not to normal cells. The mAb A10-A3 was selected and its target antigen was identified as the L1 cell adhesion molecule. Expression of L1 in ICC was evaluated by immunohistochemical analysis of tumor samples from 42 ICC patients. The functional significance of L1 expression in the tumor progression of ICC was investigated by L1 suppression, L1 overexpression, and antibody treatment. RESULTS: L1 was not expressed in normal hepatocytes and intrahepatic bile duct epithelium but highly expressed in 40.5% of ICC patients, remarkably at the invasive front of the tumors. Suppression of L1 with short hairpin RNA significantly decreased proliferation, migration, and invasion of ICC cells in vitro. Consistently, L1 overexpression in ICC cells enhanced proliferation, migration, invasion, and apoptosis resistance. In addition, L1 short hairpin RNA or anti-L1 mAb significantly reduced the tumor growth in nude mice bearing ICC xenograft. CONCLUSIONS: We identified that L1 is expressed in ICC. L1 plays an important role in the tumor progression of ICC by enhancing cell proliferation, migration, invasion, and survival. L1 may represent a novel therapeutic target for ICC.