Young Sun Yoo

Potential role of vascular smooth muscle cell-like progenitor cell therapy in the suppression of experimental abdominal aortic aneurysms

Abdominal aortic aneurysms (AAA) are a growing problem worldwide, yet there is no known medical therapy. The pathogenesis involves degradation of the elastic lamina by two combined mechanisms: increased degradation of elastin by matrix metalloproteinases (MMP) and decreased formation of elastin due to apoptosis of vascular smooth muscle cells (VSMC). In this study, we set out to examine the potential role of stem cells in the attenuation of AAA formation by inhibition of these pathogenetic mechanisms. Muscle-derived stem cells from murine skeletal muscles were isolated and stimulated with PDGF-BB in vitro for differentiation to VSMC-like progenitor cells (VSMC-PC). These cells were implanted in to elastase-induced AAAs in rats. The cell therapy group had decreased rate of aneurysm formation compared to control, and MMP expression at the genetic, protein and enzymatic level were also significantly decreased. Furthermore, direct implantation of VSMC-PCs in the intima of harvested aortas was visualized under immunofluorescent staining, suggesting that these cells were responsible for the inhibition of MMPs and consequent attenuation of AAA formation. These results show a promising role of stem cell therapy for the treatment of AAAs, and with further studies, may be able to reach clinical significance.

Midterm Results of Radiofrequency Ablation for Incompetent Small Saphenous Vein in Terms of Recanalization and Sural Neuritis

BACKGROUND Safety and effectiveness of radiofrequency ablation for incompetent small saphenous vein is not established. OBJECTIVE To report midterm clinical and ultrasonograhic results of radiofrequency ablation (RFA) for small saphenous vein (SSV) in terms of recanalization and sural neuritis. METHODS AND MATERIALS We examined 39 patients (46 limbs) who had been examined using a duplex scan more than 1 year after RFA of SSV. Postoperative clinical results, risk factors for SSV recanalization, and sural neuritis were analyzed. RESULTS CEAP score and CIVIQ2 score improved significantly in all patients (CEAP: 2.45 to 1.43 (p = .03); CIVIQ2: 25.34 to 13.21 (p = .01). SSV obliteration rate was 93.4% at 1 year and 89.1% at 2 years. Preoperative peak reflux velocity in the recanalization group (54.9 cm/s) was significantly higher (p < .01) than in the obliteration group (29.8 cm/s). Sural neuritis were detected in 12 limbs (26.1%), and median symptom duration was 3 months. The total length of RFA ablation was not different between the groups with and without postablation sural neuritis. CONCLUSION RFA is an effective and safe treatment modality for incompetent SSV. Peak reflux velocity can be a risk factor for recanalization. Length of RFA segment in SSV does not affect recanalization and postablation sural neuritis.

Muscle-Derived Stem Cells Promote Angiogenesis and Attenuate Intimal Hyperplasia in Different Murine Vascular Disease Models

Muscle-derived stem cells (MDSCs) are known to promote angiogenesis, but have never been studied in vascular diseases. We differentiated MDSCs into endothelial lineage cells in vitro by stimulation with shear stress and vascular endothelial growth factor. Such differentiated MDSCs (diff-MDSC) showed strong angiogenic potential in vitro. When tested in ischemic hindlimbs of mice, diff-MDSCs increased perfusion and decreased necrosis of the ischemic limbs, by promoting new vessel formation and by upregulating genes involved in endothelial expression. Such effects were not observed with native MDSCs (without endothelial stimulation in vitro). Diff-MDSCs were also injected into carotid arteries of rats after balloon denudation of the intima layer to induce intimal hyperplasia. The cell-treated group had significantly reduced intima-to-media thickness ratio compared to control, thus attenuating intimal hyperplasia by early re-endothelialization of the intima layer. Our findings suggest that MDSCs are a potential source of stem cell therapy for treatment of various vascular diseases, by inducing angiogenesis to improve perfusion in sites of ischemia, and by preventing intimal hyperplasia in sites of vessel injury.

Modification of a Rodent Hindlimb Model of Secondary Lymphedema: Surgical Radicality versus Radiotherapeutic Ablation

Secondary lymphedema is an intractable disease mainly caused by damage of the lymphatic system during surgery, yet studies are limited by the lack of suitable animal models. The purpose of this study was to create an improved model of secondary lymphedema in the hindlimbs of rodents with sustained effects and able to mimic human lymphedema. This was achieved by combining previously reported surgical methods and radiation to induce chronic lymphedema. Despite more radical surgical destruction of superficial and deep lymphatic vessels, surgery alone was not enough to sustain increased hindlimb volume. Radiotherapy was necessary to prolong these effects, with decreased lymphatic flow on lymphoscintigraphy, but hindlimb necrosis occurred after 4 weeks due to radiation toxicity. The applicability of this model for studies of therapeutic lymphangiogenesis was subsequently tested by injecting muscle-derived stem cells previously cocultured with the supernatant of human lymphatic endothelial cells in vitro. There was a tendency for increased lymphatic flow which significantly increased lymphatic vessel formation after cell injection, but attenuation of hindlimb volume was not observed. These results suggest that further refinement of the rodent hindlimb model is needed by titration of adequate radiation dosage, while stem cell lymphangiogenesis seems to be a promising approach.

Posterior Epidural Migration of an Extruded Lumbar Disc Mimicking a Facet Cyst : A Case Report

Dorsal extradural migration of extruded disc material is clinically uncommon. We report a rare case of posterior epidural migration of an extruded lumbar disc mimicking a facet cyst. A 32-year-old man was admitted to our institute with a 2-week history of severe low back pain and radiating pain in the left leg. The magnetic resonance (MR) images revealed a dorsally located, left-sided extradural cystic mass at the L2-3 level. The initial diagnosis was an epidural facet cyst because of the high signal intensity on MR images and its location adjacent to the facet joint. Intraoperatively, an encapsulated mass of soft tissue adherent to the dural sac was observed and excised. The pathological diagnosis was degenerated disc material. After surgery, the patient experienced complete relief from leg pain.

Recent Advances in the Development of Experimental Animal Models Mimicking Human Aortic Aneurysms.

Aortic aneurysm is a common and life-threatening disease that can cause death from rupture. Current therapeutic options are limited to surgical or endovascular procedures because no pharmacological approaches have been proven to decrease the chance of expansion or rupture. The best approach to the management of aortic aneurysm would be the understanding and prevention of the processes involved in disease occurrence, progression, and rupture. There is a need for animal models that can reproduce the pathophysiological features of human aortic aneurysm, and several such models have been studied. This review will emphasize recent advances in animal models used in the determination of mechanisms and treatments of aortic aneurysms.

Analysis of patient-dropouts from the critical pathways for gastric cancer

Purpose This study was designed to determine the factors affecting completion of critical pathway for elective gastrectomy. Methods Since 2008, a critical pathway has been applied for elective gastrectomy at Chosun University Hospital. We retrospectively analyzed 252 patients who underwent elective gastrectomies from January 2009 to April 2013. The completion rate was determined, and risk factors for patient dropout were examined. Results The completion rate of the critical pathway was 45.6% (115/252). Mean length of stay was 11.7 ± 8.6 days (8-59 days). Readmission rates were 4.4% (11/252). Causes of failure for clinical pathway were systemic complications (21/137, 15.3%), intra-abdominal complications (44/137, 32.8%), patient factors (41/137, 29.9%), and wound complications (30/137, 21.9%). There were no significant differences between the two groups in age, sex, American Society of Anesthesiologists (ASA) score, operation time, readmission, and underlying disease (P > 0.05). Body mass index (P = 0.008) and pathologic stage (P = 0.001) were significantly different between the two groups. In multivariate analysis, the conventional approach (odds ratio, 2.0), and total gastrectomy (odds ratio, 5.3) were determined to be independent risk factors to drop the critical pathway. But there were no significant differences between total and distal gastrectomy groups in age, gender, underlying diseases, ASA score, readmission, operation time, and cause of dropout (P > 0.05). Conclusion We concluded that total gastrectomy may not be suitable for the critical pathway. We suggest that the critical pathway for elective distal gastrectomy is divided 2 subgroups, according to the surgical approach.

Tracking the Fate of Muscle-derived Stem Cells: an Insight into the Distribution and Mode of Action

Purpose: To examine the fate of muscle-derived stem cells (MDSC) after injection into different host conditions and provide an insight for their mechanism of action. Materials and Methods: MDSCs differentiated in vitro towards the endothelial lineage and transfected with lentivirus tagged with green fluorescent protein (GFP) were injected into two animal models mimicking vascular diseases: hindlimb ischemia and carotid injury models. Injected cells were tracked at the site of injection and in remote organs by harvesting the respective tissues at different time intervals and performing immunofluorescent histological analyses. Stem cell survival was quantified at the site of injection for up to 4 weeks. Results: MDSCs were successfully tagged with fluorescent material GFP and showed successful implantation into the respective injection sites. These cells showed a higher affinity to implant in blood vessel walls as shown by double fluorescent co-stain with CD31. Quantification of stem cell survival showed a timede pendent decrease from day 3 to 4 weeks (survival rate normalized against day 3 was 72.0% at 1 week, 26.8% at 2 weeks and 2.4% at 4 weeks). Stem cells were also found in distant organs, especially the kidneys and liver, which survived up to 4 weeks. Conclusion: MDSCs were successfully tracked in different vascular disease models, and their fate was assessed in terms of cell survival and distribution. Better understanding of the donor cell properties, including their interaction with the host conditions and their mechanism of action, are needed to enhance cell survival and achieve improved outcomes.