A5014334441- Virus-based gene therapy research
- Herpesvirus Infections and Treatments
- Viral Infectious Diseases and Gene Expression in Insects
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Immune Cell Function and Interaction
- Mesenchymal stem cell research
- Renal and related cancers
- Insect Resistance and Genetics
- 3D Printing in Biomedical Research
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Invertebrate Immune Response Mechanisms
- Pain Mechanisms and Treatments
- Tissue Engineering and Regenerative Medicine
- Glycosylation and Glycoproteins Research
- Viral gastroenteritis research and epidemiology
- Viral Infections and Immunology Research
- Bladder and Urothelial Cancer Treatments
- Neurobiology and Insect Physiology Research
- Immunotherapy and Immune Responses
- Chronic Lymphocytic Leukemia Research
- Liver physiology and pathology
- Hematopoietic Stem Cell Transplantation
Nippon Medical School
2018-2025
University of Pittsburgh
2012-2020
Saitama Medical University
2018
Creative Research Enterprises (United States)
2018
National Center For Child Health and Development
2007-2015
National Institutes of Health
2009-2013
Kyushu University
2004-2012
National Rehabilitation Center for Persons with Disabilities
2012
Keio University
2010
Gifu University
2010
Hepatic repair is directed chiefly by the proliferation of resident mature epithelial cells. Furthermore, if predominant injury to cholangiocytes, hepatocytes can transdifferentiate cholangiocytes assist in and vice versa, as shown various fate‐tracing studies. However, molecular bases reprogramming remain elusive. Using two models biliary where occurs through cholangiocyte hepatocyte transdifferentiation we identify an important role Wnt signaling. First up‐regulation specific proteins...
Human embryonic stem cells (ESCs) and induced pluripotent (iPSCs) have the potential to differentiate into all cell lineages, including hepatocytes, in vitro. Induced hepatocytes a wide range of application biomedical research, drug discovery, treatment liver disease. However, existing protocols for hepatic differentiation PSCs are not very efficient. In this study, we developed an efficient method induce hepatoblasts, which progenitors from human ESCs iPSCs by overexpression HEX gene, is...
Glioblastoma multiforme (GBM) is an aggressive brain cancer for which there no effective treatment. Oncolytic HSV vectors (oHSVs) are attenuated lytic viruses that have shown promise in the treatment of human GBM models animals, but their efficacy early phase patient trials has been limited. Instead attenuating virus with mutations virulence genes, we engineered four copies recognition sequence miR-124 into 3'UTR essential ICP4 gene to protect healthy tissue against replication; expressed...
Significance Gene therapy has made significant strides in the treatment and even cure of single-gene defects. However, maturation this field will require more sophisticated vehicles capable cell-selective delivery large genetic payloads whose regulated expression restore or enhance cellular functionality. High-capacity herpes simplex virus vectors have potential to meet these challenges but been limited by need preserve one particularly cytotoxic viral product, infected cell polypeptide 0,...
Ewing's family tumor (EFT) is a rare pediatric of unclear origin that occurs in bone and soft tissue. Specific chromosomal translocations found EFT cause EWS to fuse subset ets transcription factor genes (ETS), generating chimeric EWS/ETS proteins. These proteins are believed play crucial role the onset progression EFT. However, mechanisms responsible for EWS/ETS-mediated remain unclear. Here we report establishment tetracycline-controlled EWS/ETS-inducible system human marrow-derived...
Practical clinical applications for current induced pluripotent stem cell (iPSC) technologies are hindered by very low generation efficiencies. Here, we demonstrate that newborn human (h) and mouse (m) extra-embryonic amnion (AM) yolk-sac (YS) cells, in which endogenous KLF4/Klf4, c-MYC/c-Myc RONIN/Ronin expressed, can be reprogrammed to hiPSCs miPSCs with efficiencies AM cells of 0.02% 0.1%, respectively. Both hiPSC indistinguishable from embryonic colony morphology, expression pluripotency...
Abstract Human trisomy 21, responsible for Down syndrome, is the most prevalent genetic cause of cognitive impairment and remains a key focus prenatal preimplantation diagnosis. However, research directed toward eliminating supernumerary chromosomes from trisomic cells limited. The present study demonstrates that allele-specific multiple chromosome cleavage by clustered regularly interspaced palindromic repeats Cas9 can achieve rescue target human 21 induced pluripotent stem fibroblasts....
Here, we report the highly efficient in vitro differentiation of human bone marrow-derived mesenchymal stem/progenitor cells (MPCs) using a novel nanotechnology-based culture plate, nanoculture plate(®) (NCP). The NCP contains uneven microfabrications with diameters ∼2-3 μm arranged honeycomb pattern on its surface, which is devoid animal-derived protein sources. When MPCs were subjected to three-dimensional (3D) an NCP, they rapidly formed adhesive spheroids. We showed that adipogenic...
Recombinant adeno-associated virus serotype 9 (rAAV9) can specifically transduce muscle and neuronal tissues; thus, rAAV9 potentially be used in gene therapy. However, is the most challenging rAAV to purify. Traditionally, has been purified by ultracentrifugation, which not scalable. We recently described a chromatographic purification protocol for rAAV1; this achieve scalable purifications. In study, we attempted optimize purifying preparations, developed novel, effective method high-yield...
Background Human induced pluripotent stem (iPS) cells are currently used as powerful resources in regenerative medicine. During very early developmental stages, DNA methylation decreases to an overall low level at the blastocyst stage, from which embryonic derived.Therefore, cells, such ES and iPS considered have hypo-methylated status compared differentiated cells. However, epigenetic mechanisms of “stemness” remain unknown derived extra-embryonic Methodology/Principal Findings We examined...
We have established a serum- and feeder-free culture system for the efficient differentiation of multifunctional hepatocytes from human embryonic stem (ES) cells three entirely different induced pluripotent (iPS) (including vector/transgene-free iPS generated using Sendai virus vector) without cell sorting gene manipulation. The differentiation-inducing protocol consisted first stage; endoderm induction, second hepatic initiation, third maturation. At end culture, expressed...
Previously we reported a new series of highly defective herpes simplex virus type 1 (HSV-1) vectors that were functionally devoid all viral immediately early (IE) genes, resulting in virtual absence gene expression. Nevertheless, reporter cassette inserted into the vector flanked by boundary elements from latency locus showed high, persistent activity non-neuronal cells while an independent expression deleted ICP4 remained almost silent. In contrast to cells, show here permitted robust...
Induced pluripotent stem cell-derived mesenchymal cells (iMSCs) hold great promise as a cell source for transplantation into injured tissues to alleviate inflammation. However, the therapeutic efficacy of iMSC ischemic stroke remains unknown. In this study, we evaluated effects on brain injury after ischemia-reperfusion using rat transient middle cerebral artery occlusion model and compared its with that bone marrow (BMMSCs). We showed iMSCs BMMSCs reduced infarct volumes reperfusion...
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 photoreceptors in retina. Neural retina iris-pigmented epithelium (IPE) share a common developmental origin, leading us to test whether iris cells could differentiate retinal We here define factor combinations that can determine photoreceptor cell fate. Expression rhodopsin, blue opsin green/red induced were...
Embryonic stem (ES) cells recapitulate normal developmental processes and serve as an attractive source for routine access to a large number of research therapies. We previously reported that ES cultured on M15 cells, or synthesized basement membrane (sBM) substratum, efficiently differentiated into endodermal fate subsequently adopted fates various digestive organs, such the pancreas liver. Here, we established novel hepatic differentiation procedure using synthetic nanofiber (sNF) cell...
Abstract Background hiPSCs are generated through epigenetic reprogramming of somatic tissue. Genomic imprinting is an phenomenon which monoallelic gene expression regulated in a parent-of-origin-specific manner. Reprogramming relies on the successful erasure marks differentiation while maintaining those required for genomic imprinting. Loss (LOI), occurs many types malignant tumors, would hinder clinical application hiPSCs. Results We examined status, levels and DNA methylation status eight...
Congenital human cytomegalovirus (HCMV) infection, a leading cause of birth defects, is most often manifested as neurological disorders. The pathogenesis HCMV-induced disorders is, however, largely unresolved, primarily because limited availability model systems to analyze the effects HCMV infection on neural cells. An induced pluripotent stem cell (iPSC) line was established from fibroblast MRC5 by introducing Yamanaka’s four factors and then differentiate into stem/progenitor cells (NSPCs)...
Background The Dickkopf (DKK) family comprises a set of proteins that function as regulators Wnt/β–catenin signaling and has crucial role in development. Recent studies have revealed the involvement this tumorigenesis, however their tumorigenesis is still remained unclear. Methodology/Principal Findings We found increased expression DKK2 but decreased DKK1 Ewing tumor (EFT) cells. showed EFT-specific EWS/ETS fusion enhance promoter activity, not via ets binding sites (EBSs) 5′ upstream...