Simple Maturation of Direct-Converted Hepatocytes Derived from Fibroblasts

Target cells differentiation techniques from stem cells are developed rapidly. Recently, direct conversion techniques are introduced in various categories. Unlike pluripotent stem cells, this technique enables direct differentiation into the other cell types such as neurons, cardiomyocytes, insulin-producing cells, and hepatocytes without going through the pluripotent stage. However, the function of these converted cells reserve an immature phenotype. Therefore, we modified the culture conditions of mouse direct converted hepatocytes (miHeps) to mature fetal characteristics, such as higher AFP and lower albumin (ALB) expression than primary hepatocytes. First, we generate miHeps from mouse embryonic fibroblasts (MEFs) with two transcription factors HNF4α and Foxa3. These cells indicate typical epithelial morphology and express hepatic proteins. To mature hepatic function, DMSO is treated during culture time for more than 7 days. After maturation, miHeps showed features of maturation such as exhibiting typical hepatocyte-like morphology, increased up-regulated ALB and CYP enzyme gene expression, down-regulated AFP expressions, and acquired hepatic function over time. Thus, our data provides a simple method to mature direct converted hepatocytes functionally and these cells enable them to move closer to generating functional hepatocytes.

Cancer Stem Cells: Biological Features and Targeted Therapeutics / 한양의대학술지

Advance in stem cells (SCs) has become significant by the isolation of the tissue-specific SCs in a tissue, because it is the beginning of using SC utility for regenerative medicine. Likewise in SCs, a small subpopulation of cancer cells, named cancer stem cells (CSCs), also have similar properties. These properties include indefinite self-renewal potential and sharing similar signaling pathways with normal SCs, because the originality of CSCs is from the mutation of normal SCs. Hierarchically, CSCs in solid tumors may organize from the normal SCs in the highest cellular hierarchy of these cancer cells. The functional assay techniques to assess the differentiation frequency of normal SCs are similarly used in CSCs to sustain tumor growth and recurrence after therapy. In this review, we discuss the different parallels between adult SCs and CSCs in solid cancer disease and applications toward targeted therapy in use of molecular level on CSCs.

Genomics in Organ Transplantation / 한양의대학술지

The understanding of genetic diversities in humans by applying the state of the art genomic technologies has been accumulated and enriched since the last decades. Even in organ transplantation, these genomic technologies have not yet been widely applied and have less impact, except Human Leukocyte Antigen (HLA) matching. Pre- and post-operative care including surgical techniques in organ transplantation has improved reducing morbidity and mortality, but there are limitations and obstacles due to personal diversities coming from genetic variation. For this reason, the therapy combined with genomic information would be promising and beneficial in organ transplantation and would expect to give a new paradigm in personalized medicine in the near future. In this review, we introduce Next Generation Sequencing (NGS) technology and summarize potential benefits of these technologies in organ transplantation.

Identification of genes underlying different methylation profiles in refractory anemia with excess blast and refractory cytopenia with multilineage dysplasia in myelodysplastic syndrome

BACKGROUND: Myelodysplastic syndrome (MDS) is a preleukemic condition that transforms into acute myeloid leukemia. However, the genetic events underlying this transformation remain poorly understood. Aberrant DNA methylation may play a causative role in the disease and its prognosis. Thus, we compared the DNA methylation profiles in refractory anemia with excess blast (RAEB) to those in refractory cytopenia with multilineage dysplasia (RCMD). METHODS: Bone marrow samples were collected from 20 patients with primary MDS (9 with RAEB and 11 with RCMD), and peripheral blood samples were collected from 4 healthy controls. These samples were assessed using a commercial whole genome-wide methylation assay. Methylation-specific polymerase chain reaction (PCR) was used to detect the methylation of candidate gene promoters in RAEB and RCMD. RESULTS: Microarray data revealed significant hypermethylation in 69 genes within RAEB but not RCMD. Candidate genes were mapped to 5 different networks, and network 1 had the highest score due to its involvement in gene expression, cancer, and cell cycle. Five genes (GSTM5, BIK, CENPH, RERG, and ANGPTL2) were associated with malignant disease progression. Among them, the methylated promoter pairs of GSTM5 (55.5% and 20%), BIK (20% and 0%), and ANGPTL2 (44.4% and 10%) were observed more frequently in RAEB. CONCLUSION: DNA methylation of GSTM5, BIK, and ANGPTL2 may induce epigenetic silencing and contribute to the increasing blasts and resulting MDS progression; however, the functions of these genes were not determined. Further study focusing on epigenetic silencing using various detection modalities is required.

Is routine nasogastric tube insertion necessary in pancreaticoduodenectomy? / 대한외과학회지

PURPOSE: The necessity of nasogastric decompression after abdominal surgical procedures has been increasingly questioned for several years. Traditionally, nasogastric decompression is a mandatory procedure after classical pancreaticoduodenectomy (PD); however, we still do not know whether or not it is necessary for PD. The present study was designed to assess the clinical benefit of nasogastric decompression after PD. METHODS: Between July 2004 and May 2007, 41 consecutive patients who underwent PD were enrolled in this study. Eighteen patients were enrolled in the nasogastric tube (NGT) group and 23 patients were enrolled in the no NGT group. RESULTS: There were no differences in the demographics, pathology, co-morbid medical conditions, and pre-operative laboratory values between the two groups. In addition, the passage of flatus (P = 0.963) and starting time of oral intake (P = 0.951) were similar in both groups. In the NGT group, 61% of the patients complained of discomfort related to the NGT. Pleural effusions were frequent in the NGT group (P = 0.037); however, other post-operative complications, such as wound dehiscence and anastomotic leakage, occurred similarly in both groups. There was one case of NGT re-insertion in the NGT group. CONCLUSION: Routine nasogastric decompression in patients undergoing PD is not mandatory because it has no clinical advantages and increases patient discomfort.