Dae Hwan Kim

Atmospheric (in vitro) oxygen pressure is around 150 mm Hg (20% O2), whereas physiologic (in vivo) oxygen pressure ranges between 5 and 50 mm Hg (0.7–7% O2). The normoxic environment in cell culture does not refer to a physiological stem cell niche. The aim of this study is to investigate the effect of oxygen concentration on cell properties of human mesenchymal stem cells (MSCs). We analyzed cell proliferation rate, senescence, immunophenotype, stemness gene expression and differentiation potency with human urine stem cells (USCs), dental pulp stem cells (DPSCs), amniotic fluid stem cells (AFSCs), and bone marrow stromal cells (BMSCs). USCs, DPSCs, AFSCs and BMSCs were cultured under either 5% O2 hypoxic or 20% O2 normoxic conditions for 5 days. MSCs cultured under hypoxia showed significantly increased proliferation rate and high percentage of S-phase cells, compared to normoxic condition. In real-time PCR assay, the cells cultured under hypoxia expressed higher level of Oct4, C-Myc, Nanog, Nestin and HIF-1α. In immunophenotype analysis, MSCs cultured under hypoxia maintained higher level of the MSC surface markers, and lower hematopoietic markers. Senescence was inhibited under hypoxia. Hypoxia enhances osteogenic differentiation efficiency compared to normoxia. Hypoxia showed enhanced cell proliferation rate, retention of stem cell properties, inhibition of senescence, and increased differentiation ability compared to normoxia.

Lymphocytes cross vascular boundaries via either disrupted tight junctions (TJs) or caveolae to induce tissue inflammation. In the CNS, Th17 lymphocytes cross the blood-brain barrier (BBB) before Th1 cells; yet this differential crossing is poorly understood. We have used intravital two-photon imaging of the spinal cord in wild-type and caveolae-deficient mice with fluorescently labeled endothelial tight junctions to determine how tight junction remodeling and caveolae regulate CNS entry of lymphocytes during the experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis. We find that dynamic tight junction remodeling occurs early in EAE but does not depend upon caveolar transport. Moreover, Th1, but not Th17, lymphocytes are significantly reduced in the inflamed CNS of mice lacking caveolae. Therefore, tight junction remodeling facilitates Th17 migration across the BBB, whereas caveolae promote Th1 entry into the CNS. Moreover, therapies that target both tight junction degradation and caveolar transcytosis may limit lymphocyte infiltration during inflammation.

Although the vast majority of gastrointestinal (GI) masses are epithelial neoplasms, a variety of subepithelial masses are infrequently encountered during endoscopic or radiologic examination. A subepithelial mass, which was previously called a submucosal mass, is defined as a mass covered with normal-appearing mucosa, whether the underlying process is intramural or extramural in origin. At contrast material-enhanced computed tomography (CT), hypervascular subepithelial masses are usually detected more easily than isoattenuating or hypovascular masses. Entities that appear as intramural hypervascular subepithelial lesions include neuroendocrine tumors, GI stromal tumor, glomus tumor, hemangioma, angiosarcoma, Kaposi sarcoma, nerve sheath tumors, hypervascular metastases, heterotopic tissues, and vascular structures. Entities that appear as extramural hypervascular subepithelial lesions include Castleman disease, solitary fibrous tumor, inflammatory myofibroblastic tumor, and actinomycosis. Some rare gastric cancers resemble subepithelial tumors. In comparison with endoscopic ultrasonography, CT is of limited value in differentiating the layers of the GI wall and determining the origin of mass lesions. However, recent advances in multidetector CT with multiplanar reformation allow one to determine whether a GI mass is of epithelial, intramural subepithelial, or extramural subepithelial origin. Furthermore, the full extent of tumors can be delineated, and local invasion and distant metastases can be identified. Familiarity with the characteristic CT appearances of hypervascular subepithelial masses of the GI tract will help radiologists make a more confident diagnosis.