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Park S.-J.,Tokyo Medical University | Komiyama Y.,Tokyo Medical University | Suemori H.,Kyoto University | Umezawa A.,National Institute for Child Health and Development | Nakai K.,Tokyo Medical University
Nucleic Acids Research

Human stem cells are promising sources for regenerative therapy. To ensure safety of future therapeutic applications, the differentiation potency of stem cells has to be tested and be widely opened to the public. The potency is generally assessed by teratoma formation comprising differentiated cells from all three germ layers, and the teratomas can be inspected through high-quality digital images. The teratoma assay, however, lacks consistency in transplantation protocols and even in interpretation, which needs community-based efforts for improving the assay quality. Here, we have developed a novel database OpenTein (Open Teratoma Investigation, http://opentein.hgc.jp/) to archive and freely distribute high-resolution whole-slide images and relevant records. OpenTein has been designed as a searchable, zoomable and annotatable web-based repository system. We have deposited 468 images of teratomas derived by our transplantation of human stem cells, and users can freely access and process such digital teratoma images. Approximately, the current version of OpenTein responds within 11.2min for processing 2.03 gigapixel teratoma images. Our system offers valuable tools and resources in the new era of stem cell biology. © The Author(s) 2015. Source

Umezawa A.,National Institute for Child Health and Development
Laboratory Investigation

The two leading models that have been used to explain tumor progression in head and neck squamous cell carcinoma (HNSCC) are the stochastic clonal evolution model, in which many tumor cells are individually capable of recapitulating the entire tumor mass, and the cancer stem hierarchy model, in which only rare totipotential tumor stem cells can recapitulate the tumor. In this issue, Cameron et al use cell surface marker and clonal cell analyses in combination with a xenotransplant approach to provide data that support the stochastic clonal evolution model in HNSCC. This interpretation is subject, however, to limitations inherent in the experimental approach employed. Understanding the basis of tumor progression in HNSCC as well as other cancers should be further explored because of important implications for effective treatments. © 2010 USCAP, Inc All rights reserved. Source

Inoue T.,Saitama University | Umezawa A.,National Institute for Child Health and Development | Takenaka T.,Saitama University | Suzuki H.,Saitama University | Okada H.,Saitama University
Kidney International

The impact of The epithelial-mesenchymal transition (EMT) to The formation of renal fibrosis has been debated in several lineage-tracing studies, with conflicting findings. Such disparities may have arisen from varying experimental conditions such as different disease models, The mouse strain, and type of genetic alteration used. In order to determine The contribution of these factors to EMT, we generated four kidney disease models in several mouse strains genetically modified to express enhanced green fluorescence protein (EGFP) in cortical tubular epithelial cells under The control of The γ-glutamyl transpeptidase promoter. Using this approach, The EMT was visible and quantifiable based on a count of EGFP-positive interstitial cells in The fibrotic kidney sections of The four renal disease models found to be either EMT-prone or-resistant. The EMT-prone models consisted of unilateral ureteral obstruction and ischemic nephropathy in SJL mice. The EMT-resistant models consisted of ureteral obstruction in C57B/6 and F1(C57B/6 × SJL) mice, adriamycin nephrosis in 129 mice, and nephrotoxic serum nephritis in SJL mice. Analyses of these renal disease models suggest The emergence of EMT-derived fibroblasts arises in a disease-specific and strain-dependent manner. Thus, when considering molecular mechanisms and involvement of The EMT in renal fibrosis, it is important to take into account The experimental conditions, particularly The mouse strain and type of disease model. © 2015 International Society of Nephrology. Source

Examples of direct differentiation by defined transcription factors have been provided for beta-cells, cardiomyocytes and neurons. In the human visual system, there are four kinds of photoreceptors in the retina. Neural retina and iris-pigmented epithelium (IPE) share a common developmental origin, leading us to test whether human iris cells could differentiate to retinal neurons. We here define the transcription factor combinations that can determine human photoreceptor cell fate. Expression of rhodopsin, blue opsin and green/red opsin in induced photoreceptor cells were dependent on combinations of transcription factors: A combination of CRX and NEUROD induced rhodopsin and blue opsin, but did not induce green opsin; a combination of CRX and RX induced blue opsin and green/red opsin, but did not induce rhodopsin. Phototransduction-related genes as well as opsin genes were up-regulated in those cells. Functional analysis; i.e. patch clamp recordings, clearly revealed that generated photoreceptor cells, induced by CRX, RX and NEUROD, responded to light. The response was an inward current instead of the typical outward current. These data suggest that photosensitive photoreceptor cells can be generated by combinations of transcription factors. The combination of CRX and RX generate immature photoreceptors: and additional NEUROD promotes maturation. These findings contribute substantially to a major advance toward eventual cell-based therapy for retinal degenerative diseases. Source

Gojo S.,University of Tokyo | Toyoda M.,Tokyo Metropolitan University | Umezawa A.,National Institute for Child Health and Development
Journal of Artificial Organs

Research in order that artificial organs can supplement or completely replace the functions of impaired or damaged tissues and internal organs has been underway for many years. The recent clinical development of implantable left ventricular assist devices has revolutionized the treatment of patients with heart failure. The emerging field of regenerative medicine, which uses human cells and tissues to regenerate internal organs, is now advancing from basic and clinical research to clinical application. In this review, we focus on the novel biomaterials, i.e., fusion protein, and approaches such as three-dimensional and whole-organ tissue engineering. We also compare induced pluripotent stem cells, directly reprogrammed cardiomyocytes, and somatic stem cells for cell source of future cell-based therapy. Integrated strategy of artificial organ and tissue engineering/regenerative medicine should give rise to a new era of medical treatment to organ failure. © 2011 The Japanese Society for Artificial Organs. Source

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