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Huang H.-I.,Chang Gung University | Chen S.-K.,Cathay Medical Research Institute | Ling Q.-D.,Cathay Medical Research Institute | Ling Q.-D.,National Central University | And 4 more authors.
Tissue Engineering - Part A | Year: 2010

Adult stem cells that reside in adult tissues have been deemed to possess great potential for clinical application because of their capabilities of self-renewal and differentiation. However, the limitations such as infection risks and low isolation rate make the search for appropriate source to be continued. Here, we demonstrate isolation of progenitors from human foreskin tissue samples, which have fibroblast-like morphology and could be easily propagated for more than 50 passages. These foreskin-derived fibroblast-like stromal cells (FDSCs) expressed CD90, CD105, CD166, CD73, SH3, and SH4, which is similar to the immunophenotypes of human bone marrow-derived mesenchymal stem cells. In comparison with Hs68, the human fibroblast cell line, FDSCs are positive for CD105 and absent for CD54 expression. Further, FDSCs could be induced to differentiate into osteocytes, adipocytes, neural cells, smooth muscle cells, Schwann-like cells, and hepatocyte-like cells. Interestingly, when cultured in Dulbecco's modified Eagle's medium/F12 medium, FDSCs can form spheres with increased expression levels of fibronectin and vimentin. In conclusion, foreskin can serve as a valuable source of multipotent cells with the capabilities for endodermal, mesodermal, and ectodermal cells. Coupled with the advantages of their easy access, isolation, and propagation, these foreskin-derived stromal cells might be of potential use in future studies in stem cell differentiation and therapeutic application. © 2010 Mary Ann Liebert, Inc.

Chung C.A.,National Central University | Lin T.-H.,National Central University | Chen S.-D.,National Central University | Huang H.-I.,Cathay Medical Research Institute
Journal of Theoretical Biology | Year: 2010

Mathematic models help interpret experimental results and accelerate tissue engineering developments. We develop in this paper a hybrid cellular automata model that combines the differential nutrient transport equation to investigate the nutrient limited cell construct development for cartilage tissue engineering. Individual cell behaviors of migration, contact inhibition and cell collision, coupled with the cell proliferation regulated by oxygen concentration were carefully studied. Simplified two-dimensional simulations were performed. Using this model, we investigated the influence of cell migration speed on the overall cell growth within in vitro cell scaffolds. It was found that intense cell motility can enhance initial cell growth rates. However, since cell growth is also significantly modulated by the nutrient contents, intense cell motility with conventional uniform cell seeding method may lead to declined cell growth in the final time because concentrated cell population has been growing around the scaffold periphery to block the nutrient transport from outside culture media. Therefore, homogeneous cell seeding may not be a good way of gaining large and uniform cell densities for the final results. We then compared cell growth in scaffolds with various seeding modes, and proposed a seeding mode with cells initially residing in the middle area of the scaffold that may efficiently reduce the nutrient blockage and result in a better cell amount and uniform cell distribution for tissue engineering construct developments. © 2009 Elsevier Ltd. All rights reserved.

Yang S.H.,Taipei Veterans General Hospital | Yang S.H.,National Yang Ming University | Huang C.-J.,Cathay Medical Research Institute | Chang S.-C.,Taipei Veterans General Hospital | And 3 more authors.
Annals of Surgical Oncology | Year: 2011

Background. An elevated plasma level of C-reactive protein (CRP) is a risk for, and prognostic factor of, colorectal cancer (CRC). In other reports of CRP concerning cardiovascular disease, CRP level correlated with its gene polymorphisms. We hypothesized that CRP polymorphisms associate risk and prognosis of CRC. Methods. This study enrolled 421 patients with CRC and 218 healthy control subjects. After preliminary studies, we selected four single nucleotide polymorphisms (SNPs) in the CRP gene: +2147A>G (rs1205), +942G>C (rs1800947), -717A>G (rs2794521), and -757T>C (rs3093059). At first, analyzing distributions of four SNPs between CRC case and non-CRC control groups was performed. Subsequently, the impacts of these SNPs with other prognostic factors of disease-free interval (DFI) and cancer-specific survival (CSS) were analyzed using uniand multivariate Cox regression analyses. Results. The case and control groups differed in the frequency of -757T>C (P = 0.002). The CRC case group had a higher percentage of the TT genotype (odds, 1.75). Regarding prognoses, multivariate analyses revealed that four factors, including stage (I, II, III), gross tumor type (polypoid, ulcerative, infiltrative), location (right, left, rectum), and -757T>C SNP (odds, 1.29; P = 0.048), correlated with DFI; two factors, including stage and +2147A>G SNP (odds, 0.71; P = 0.03), correlated with CSS. Conclusions. The -757T>C SNP is a risk for and prognostic factor of DFI; the +2147A>G SNP is a prognostic factor of CSS. CRP polymorphisms associate the risk and survival of CRC. © Society of Surgical Oncology 2011.

Lin S.-C.,Cathay General Hospital | Lin S.-C.,Cathay Medical Research Institute | Lin S.-C.,Fu Jen Catholic University | Kuo C.-C.,Cathay General Hospital | And 2 more authors.
European Journal of Clinical Investigation | Year: 2012

Background Interleukin (IL)-28 is an interferon-λ-family member involved in immunity against viral infection and tumour. We here determined the expression profiles of IL-28 and IL-28 receptor α (IL-28RA) in patients with systemic lupus erythematosus (SLE) to evaluate the possibility that IL-28 is linked to the pathogenesis of SLE. Materials and methods The serum IL-28 protein levels were determined by ELISA, and the IL-28 and IL-28RA transcript levels in peripheral blood mononuclear cells (PBMCs) and peripheral blood T cells were determined by RT-PCR. The levels in patients with SLE with the active disease activity were statistically compared with those in normal controls. Results IL-28 protein in sera and IL-28 transcripts in PBMCs and unactivated T cells were detectable only in some individuals, and IL-28 transcripts in T cells were induced by cell activation with anti-CD2, anti-CD3 and anti-CD28 antibodies. However, compared with normal controls, patients with SLE more frequently had detectable IL-28 protein in serum and had the higher IL-28 transcript levels in activated CD4 + T cells, but not activated CD8 + T cells. Two IL-28RA transcripts isoforms were detected in PBMCs and T cells, and their levels in patients with SLE were comparable with those in normal controls. Conclusions The expression of IL-28, a T-cell autocrine factor, is dysregulated in patients with SLE, supporting the possibility that IL-28 may contribute to some of the SLE pathogenesis. © 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.

Higuchi A.,National Central University | Higuchi A.,National Health Research Institute | Higuchi A.,Cathay Medical Research Institute | Tamai M.,Tokyo Institute of Technology | And 8 more authors.
Polymer Reviews | Year: 2010

The optical resolution or chiral separation of one specific enantiomer from others is in demand for the production of pharmaceuticals because many pharmaceuticals exist as stereoisomers, with each enantiomer having different biological activity. There is considerable demand for separation techniques appropriate for the large-scale resolution of chiral molecules. Chiral separation of racemic mixtures of pharmaceuticals through chiral or achiral polymeric membranes with or without a chiral selector represents a promising system for future commercial application. This article reviews several polymeric materials for the chiral separation of pharmaceuticals. Several chiral separation membranes were prepared from chiral polymers where enantioselectivity was generated from chiral carbons in the main chain. However, it is rather difficult to generate excellent chiral separation membranes from chiral polymers alone, because racemic penetrants mainly encounter the flexible side chains of the membrane polymers. Therefore, chiral separation membranes were also prepared using polymers with a chiral branch. Furthermore, several molecules have been used for specific interactions between the molecules and specific pharmaceuticals or drugs in chiral separation membranes. Cyclodextrins, crown ether derivatives, albumin, and DNA are commonly used as stereoselective ligands in chiral separation membranes. Finally, this article discusses future trends in polymeric materials for chiral separation membranes.

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