Patterns of renal disease in South Korea: a 20-year review of a single-center renal biopsy database.

BACKGROUND: Several registries and centers have reported the results of renal biopsies from different parts of the world. As there are few data regarding the epidemiology of glomerulonephritis (GN) in South Korea, we conducted this study on renal biopsy findings during the last 20 years from a single center. METHODS: Data for 818 patients who underwent renal biopsy at our center between 1992 and 2011 were collected retrospectively. All kidney specimens were examined with light microscopy (LM) and immunofluorescent microscopy (IF). RESULTS: There were 818 cases of native kidney biopsies. In cases of primary GN, the most frequent type of renal pathology in adults (18-59 years) was mesangial proliferative GN (MsPGN, 34.5%) followed by IgA nephropathy (IgAN, 33.3%) and membranous GN (MGN, 8.8%). Indications in adults (18-59 years) were asymptomatic urinary abnormalities (75.3%) followed by nephrotic syndrome (19.8%) and acute kidney injury (AKI, 3.4%). CONCLUSIONS: Among 818 renal biopsy specimens, MsPGN and IgAN were the most frequent biopsy-proven renal diseases. MGN was the third most common cause of primary GN and lupus nephritis (LN) was the most common secondary glomerular disease. Our data contribute to the epidemiology of renal disease in South Korea.

Regeneration of peripheral nerves by transplanted sphere of human mesenchymal stem cells derived from embryonic stem cells.

In cell therapy, the most important factor for therapeutic efficacy is the stable supply of cells with best engraftment efficiency. To meet this requirement, we have developed a culture strategy such as three-dimensional sphere of human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) in serum-free medium. To investigate the in vivo therapeutic efficacy of hESC-MSC spheres in nerve injury model, we transected the sciatic nerve in athymic nude mice and created a 2-mm gap. Transplantation of hESC-MSC as sphere repaired the injured nerve significantly better than transplantation of hESC-MSC as suspended single cells in regard to 1) nerve conduction (sphere; 28.81 ± 3.55 vs. single cells; 18.04 ± 2.10, p < 0.05) and 2) susceptibility of nerve stimulation at low voltage (sphere; 0.38 ± 0.08 vs. single cells; 0.66 ± 0.11, p < 0.05) at 8 weeks. Recovery after sphere transplantation was near-complete when compared with the data of normal control (sphere 28.81 ± 3.55 vs normal 32.62 ± 2.85 in nerve conduction : sphere 0.38 ± 0.08 vs normal 0.36 ± 0.67 in susceptibility of nerve stimulation, no significant difference, respectively). Recovery in function of the injured nerve was well corroborated by the histologic evidence of regenerated nerve. In the mechanistic analysis, the supernatant of sphere-forming hESC-MSC contains hepatocyte growth factor and insulin-like growth factor-binding protein-1 significantly more than the supernatant of the single cells of hESC-MSC has, which might be the key factors for the improved engraftment efficiency and greater regeneration of injured peripheral nerve.

Spherical bullet formation via E-cadherin promotes therapeutic potency of mesenchymal stem cells derived from human umbilical cord blood for myocardial infarction.

The beneficial effects of stem cells in clinical applications to date have been modest, and studies have reported that poor engraftment might be an important reason. As a strategy to overcome such a hurdle, we developed the spheroid three dimensional (3D) bullet as a delivery method for human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) through the maintenance of cell-cell interactions without additional xenofactors, cytokines, or matrix. We made spheroid 3D-bullets from hUCB-MSCs at 24 hours' anchorage-deprived suspension culture. To investigate the in vivo therapeutic efficacy of 3D-bullets, we used rat myocardial infarction (MI) model. Transplantation of 3D-bullet was better than that of single cells from monolayer culture or from 3D-bullet in improving left ventricular (LV) contractility [LV ejection fraction (LVEF) or LV fractional shortening (LVFS)] and preventing pathologic LV dilatation [LV end-systolic diameter (LVESD) or LV end-diastolic diameter (LVEDD)] at 8 weeks. In the mechanism study of 3D-bullet formation, we found that calcium-dependent cell-cell interaction was essential and that E-cadherin is a key inducer mediating hUCB-MSC 3D-bullet formation among several calcium-dependent adhesion molecules which were nominated as candidates after cDNA array analysis. In more specific experiments with E-cadherin overexpression using adenoviral vector or with E-cadherin neutralization using blocking antibody, we found that E-cadherin regulates vascular endothelial growth factor (VEGF) secretion via extracellular signal-regulated kinase (ERK)/v-akt murine thymoma viral oncogene homolog1 (AKT) pathways. During formation of spheroid 3D-bullets, activation of E-cadherin in association with cell-cell interaction turns on ERK/AKT signaling pathway that are essential to proliferative and paracrine activity of MSCs leading to the enhanced therapeutic efficacy.

N-cadherin determines individual variations in the therapeutic efficacy of human umbilical cord blood-derived mesenchymal stem cells in a rat model of myocardial infarction.

In this study, we established and characterized human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) from four different donors. However, the hUCB-MSCs showed remarkable variations in their therapeutic efficacy for repairing rat infarcted myocardium (including the process of angiogenesis) 8 weeks after transplantation. In addition, we observed that the level of vascular endothelial growth factor (VEGF) is correlated with the therapeutic efficacy of the four hUCB-MSCs. Next, to investigate the practical application of hUCB-MSCs, we searched for surface signature molecules that could serve as indicators of therapeutic efficacy. The gene for N-cadherin was the only cell surface gene that was highly expressed in the most effective hUCB-MSCs, both at the transcriptional and translational levels. We observed downregulation and upregulation of VEGF in response to N-cadherin blocking and N-cadherin overexpression, respectively. Activation of extracellular signal-regulated kinase (ERK), but not protein kinase B, was increased when N-cadherin expression was increased, whereas disruption of N-cadherin-mediated cell-cell contact induced suppression of ERK activation and led to VEGF downregulation. Moreover, by investigating hUCB-MSCs overexpressing N-cadherin or N-cadherin knockdown hUCB-MSCs, we confirmed the in vivo function of N-cadherin. In addition, we observed that DiI-labeled hUCB-MSCs express N-cadherin in the peri-infarct area and interact with cardiomyocytes.