A5101020970- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Renal and related cancers
- Animal Genetics and Reproduction
- RNA Interference and Gene Delivery
- Tissue Engineering and Regenerative Medicine
- Reproductive Biology and Fertility
- Pancreatic function and diabetes
- Congenital heart defects research
- Developmental Biology and Gene Regulation
- Sperm and Testicular Function
- Congenital limb and hand anomalies
- Biomedical Ethics and Regulation
- 3D Printing in Biomedical Research
- Wound Healing and Treatments
- Metabolism, Diabetes, and Cancer
- Cancer-related molecular mechanisms research
- Planarian Biology and Electrostimulation
- Diabetes and associated disorders
- Genomics and Chromatin Dynamics
- Mesenchymal stem cell research
- Bone Tumor Diagnosis and Treatments
- Genetic Syndromes and Imprinting
- Amyotrophic Lateral Sclerosis Research
- Muscle Physiology and Disorders
Tokyo Metropolitan Institute of Medical Science
2025
Tokyo University of Science
2014-2025
The University of Tokyo
2016-2025
Tokyo Medical and Dental University
2022-2025
Japan Science and Technology Agency
2012-2017
Regenerative Medicine Institute
2015
KKR Tohoku Kosai Hospital
2011
Bayer (Japan)
2008
Tohoku University
2007
Nippon Institute for Biological Science
2001
In vitro generation of hematopoietic stem cells (HSCs) from induced pluripotent (iPSCs) has the potential to provide novel therapeutic approaches for replacing bone marrow (BM) transplantation without rejection or graft versus host disease. Hitherto, however, it proved difficult generate truly functional HSCs transplantable adult mice. Here, we demonstrate a unique in vivo differentiation system yielding engraftable mouse and human iPSCs teratoma-bearing animals combination with maneuver...
Abstract Regeneration of human kidneys in animal models would help combat the severe shortage donors transplantation therapy. Previously, we demonstrated by interspecific blastocyst complementation between mouse and rats, generation pluripotent stem cell (PSC)-derived functional pancreas, apancreatic Pdx1 mutant mice. We, however, were unable to obtain rat PSC-derived anephric Sall1 mice, likely due poor contribution PSCs metanephric mesenchyme, a nephron progenitor. Here, conversely, show...
ABSTRACT Despite four decades of effort, robust propagation pluripotent stem cells from livestock animals remains challenging. The requirements for self-renewal are unclear and the relationship cultured to resident in embryo uncertain. Here, we avoided using feeder or serum factors provide a defined culture microenvironment. We show that combination activin A, fibroblast growth factor Wnt inhibitor XAV939 (AFX) supports establishment continuous expansion cell lines porcine, ovine bovine...
Abstract Recently, several studies using cultures of human embryos together with single-cell RNA-seq analyses have revealed differences between humans and mice, necessitating the study 1–8 . Despite importance embryology, ethical legal restrictions limited post-implantation-stage studies. Thus, recent efforts focused on developing in vitro self-organizing models stem cells 9–17 Here, we report genetic non-genetic approaches to generate authentic hypoblast (naive hPSC-derived hypoblast-like...
Pluripotent stem cells are a promising tool for mechanistic studies of tissue development, drug screening, and cell-based therapies.Here, we report an effective mass-producing strategy the stepwise differentiation mouse embryonic (mESCs) human induced pluripotent (miPSCs hiPSCs, respectively) into osteoblasts using four small molecules (CHIR99021 [CHIR], cyclopamine [Cyc], smoothened agonist [SAG], helioxanthin-derivative 4-(4-methoxyphenyl)pyrido[4 0 ,3 :4,5]thieno...
In the case of organ transplantation accompanied by vascular anastomosis, major histocompatibility complex mismatched endothelial cells become a target for graft rejection. Production rejection-free, transplantable organ, therefore, requires simultaneous generation within organ. To generate pluripotent stem cell (PSC)-derived cells, we performed blastocyst complementation with growth factor receptor-2 homozygous mutant blastocyst. This mutation is embryonic lethal at (E) day 8.5–9.5 due to...
We have previously established a concept of developing exogenic pancreas in genetically modified pig fetus with an apancreatic trait, thereby proposing the possibility vivo generation functional human organs xenogenic large animals. In this study, we aimed to demonstrate further proof-of-concept compensation for disabled organogeneses pig, including pancreatogenesis, nephrogenesis, hepatogenesis, and vasculogenesis. These dysorganogenetic phenotypes could be efficiently induced via genome...
Autologous skin grafting is a standard treatment for defects such as burns. No artificial substitutes are functionally equivalent to autologous grafts. The cultured epidermis lacks the dermis and does not engraft deep wounds. Although reconstituted skin, which consists of epidermal cells on synthetic dermal substitute, can wounds, it requires wound bed be well-vascularized appendages. In this study, we successfully generate complete grafts with pluripotent stem cell-derived appendages p63...
Functional assay limitations are an emerging issue in characterizing human pluripotent stem cells (PSCs). With rodent PSCs, chimera formation using pre-implantation embryos is the gold-standard of pluripotency (competence progeny to differentiate into all three germ layers). In PSCs (hPSCs), however, this can only be monitored via teratoma or vitro differentiation, as ethical concerns preclude generation human-human human-animal chimeras. To circumvent issue, we developed a functional...
Mammalians have a low potency for limb regeneration compared to that of amphibians. One explanation the is deficiency cells regenerating amputated limbs in mammals. Amphibians can form blastema with dedifferentiated cells, but mammals few such cells. In this paper, we report formation, especially bone/cartilage formation limbs, because basic step pattern regeneration. After amputation neonatal mouse, hypertrophy stump bone was observed at site, which preceded by cell proliferation and...
Induced pluripotent stem cells (iPSCs) are a promising cell source for cartilage regenerative medicine. Meanwhile, the risk of tumorigenesis should be considered in clinical application human iPSCs (hiPSCs). Here, we report vitro chondrogenic differentiation hiPSCs and maturation differentiated through transplantation into mouse knee joints. Three hiPSC clones showed efficient using an established protocol embryonic cells. The formed hyaline tissues at 8 weeks after articular NOD/SCID...
A simple induction protocol to differentiate chondrocytes from pluripotent stem cells (PSCs) using small-molecule compounds is beneficial for cartilage regenerative medicine and mechanistic studies of chondrogenesis. Here, we demonstrate that are robustly induced human PSCs by combination two compounds, CHIR99021, a glycogen synthase kinase 3 inhibitor, TTNPB, retinoic acid receptor (RAR) agonist, under serum- feeder-free conditions within 5–9 days. An excellent differentiation efficiency...
To study development of the conceptus in xenogeneic environments, we assessed interspecies chimera formation as well tetraploid complementation between mouse and rat. Overall contribution donor PSC-derived cells was lower chimeras than intraspecies chimeras, high chimerism associated with anomalies or embryonic death. Organ to organ variation greater suggesting species-specific affinity differences among interacting molecules necessary for organogenesis. In complementation, embryo near...
Inter-cellular transmission of mRNA is being explored in mammalian species using immortal cell lines (1-3). Here, we uncover an inter-cellular transfer phenomenon that allows for the adaptation and reprogramming human primed pluripotent stem cells (hPSCs). This process induced by direct contact-mediated coculture with mouse embryonic (mESCs) under condition impermissible PSC culture. Mouse-derived contents are transmitted into adapted hPSCs only coculture. Transfer-specific analysis show...
Naive pluripotent stem cells (PSCs) are counterparts of early epiblast in the mammalian embryo. Mouse and human naive PSCs differ self-renewal requirements extraembryonic lineage potency. Here, we investigated generation chimpanzee PSCs. Colonies generated by resetting or reprogramming failed to propagate. We discovered that is enabled inhibition Polycomb repressive complex 2 (PRC2). Expanded show global transcriptome proximity embryo pre-implantation epiblast, with shared expression a...
Fair comparison of reprogramming efficiencies and in vitro differentiation capabilities among induced pluripotent stem cell (iPSC) lines has been hampered by the cellular genetic heterogeneity de novo infected somatic cells. In order to address this problem, we constructed a single cassette all-in-one inducible lentiviral vector (Ai-LV) for expression three factors (Oct3/4, Klf4 Sox2). To obtain multiple types cells having same background, generated reprogrammable chimeric mice using iPSCs...
Epiblast stem cells (EpiSCs) in mice and rats are primed pluripotent (PSCs). They barely contribute to chimeric embryos when injected into blastocysts. Reprogramming of EpiSCs embryonic cell (ESC)-like (rESCs) may occur response LIF-STAT3 signaling; however, low reprogramming efficiency hampers potential use rESCs generating chimeras. Here, we describe dramatic improvement conversion from naive-like PSCs through upregulation E-cadherin the presence cytokine LIF. Analysis revealed that...
Interspecies chimeric assays are a valuable tool for investigating the potential of human stem and progenitor cells, as well their differentiated progeny. This Spotlight article discusses different factors that affect interspecies chimera generation, such evolutionary distance, developmental timing, apoptosis transplanted suggests some possible strategies to address them. A refined approach generating chimeras could contribute not only better understanding cellular potential, but also nature...
Patients with permanent hypoparathyroidism require lifelong replacement therapy to avoid life-threatening complications, The benefits of conventional treatment are limited, however. Transplanting a functional parathyroid gland (PTG) would yield better results. Parathyroid cells generated from pluripotent stem in vitro date cannot mimic the physiological responses extracellular calcium that essential for homeostasis. We thus hypothesized blastocyst complementation (BC) could be strategy...