Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Tatsuo S. Hamazaki is active.

Publication


Featured researches published by Tatsuo S. Hamazaki.


Stem Cells | 2005

Characterization and Localization of Side Population Cells in Mouse Skin

Shoichiro Yano; Yuriko Ito; Manabu Fujimoto; Tatsuo S. Hamazaki; Kunihiko Tamaki; Hitoshi Okochi

Recently, the detection of side population (SP) cells, which have the ability to strongly efflux Hoechst 33342 fluorescence dye, has attracted attention as a method of stem cell isolation. We identified SP cells from mouse skin using the same method as from bone marrow. This population almost completely disappeared after treatment with the calcium channel blocker verapamil. SP cells were mainly localized in the epidermis, with a few in the dermis. The ratio of SP cells decreased as the mouse became older. Surface marker analysis revealed that the sorted SP cells expressed α6‐integrin, β1‐integrin, Sca‐1, keratin 14, and keratin 19, which are proliferating and progenitor cell markers, at levels higher than in non‐SP cells, while they expressed E‐cadherin, CD34, and CD71 at lower levels. The expression of breast cancer resistance protein 1 (BCRP1), which participates in dye efflux, was expressed at high levels at both the protein and mRNA level in sorted SP cells. Immunohistochemical analysis showed that BCRP1 was expressed in the basal layers and hair bulge regions of mouse skin. BCRP1 mRNA was found in basal layers and hair follicles of newborn skin by in situ hybridization. These results indicate that the localization of BCRP1‐positive cells is compatible with that of keratinocyte stem cells. Based on the close relationship between BCRP1 and the SP cell phenotype, we conclude that keratinocyte stem cells are closely related to the SP‐ or BCRP1‐positive cells.


The International Journal of Developmental Biology | 2010

Pdx1-transfected adipose tissue-derived stem cells differentiate into insulin-producing cells in vivo and reduce hyperglycemia in diabetic mice

Hiromitsu Kajiyama; Tatsuo S. Hamazaki; Makoto Tokuhara; Shinji Masui; Koji Okabayashi; Kiyoshi Ohnuma; Shigeharu Yabe; Kazuki Yasuda; Shoichi Ishiura; Hitoshi Okochi; Makoto Asashima

Insulin-dependent diabetes mellitus (IDDM) is characterized by the rapid development of potentially severe metabolic abnormalities resulting from insulin deficiency. The transplantation of insulin-producing cells is a promising approach for the treatment of IDDM. The transcription factor pancreatic duodenal homeobox 1 (Pdx1) plays an important role in the differentiation of pancreatic beta cells. In this study, the human Pdx1 gene was transduced and expressed in murine adipose tissue-derived stem cells (ASCs). To evaluate pancreatic repair, we used a mouse model of pancreatic damage resulting in hyperglycemia, which involves injection of mice with streptozotocin (STZ). STZ-treated mice transplanted with Pdx1-transduced ASCs (Pdx1-ASCs) showed significantly decreased blood glucose levels and increased survival, when compared with control mice. While stable expression of Pdx1 in ASCs did not induce the pancreatic phenotype in vitro in our experiment, the transplanted stem cells became engrafted in the pancreas, wherein they expressed insulin and C-peptide, which is a marker of insulin-producing cells. These results suggest that Pdx1-ASCs are stably engrafted in the pancreas, acquire a functional beta-cell phenotype, and partially restore pancreatic function in vivo. The ease and safety associated with extirpating high numbers of cells from adipose tissues support the applicability of this system to developing a new cell therapy for IDDM.


Biochemical and Biophysical Research Communications | 2010

Efficiently differentiating vascular endothelial cells from adipose tissue-derived mesenchymal stem cells in serum-free culture

Masamitsu Konno; Tatsuo S. Hamazaki; Satsuki Fukuda; Makoto Tokuhara; Hideho Uchiyama; Hitoshi Okazawa; Hitoshi Okochi; Makoto Asashima

Adipose tissue-derived mesenchymal stem cells (ASCs) have been reported to be multipotent and to differentiate into various cell types, including osteocytes, adipocytes, chondrocytes, and neural cells. Recently, many authors have reported that ASCs are also able to differentiate into vascular endothelial cells (VECs) in vitro. However, these reports included the use of medium containing fetal bovine serum for endothelial differentiation. In the present study, we have developed a novel method for differentiating mouse ASCs into VECs under serum-free conditions. After the differentiation culture, over 80% of the cells expressed vascular endothelial-specific marker proteins and could take up low-density lipoprotein in vitro. This protocol should be helpful in clarifying the mechanisms of ASC differentiation into the VSC lineage.


Stem Cells | 2006

Ciliated Cells Differentiated from Mouse Embryonic Stem Cells

Yusuke Nishimura; Tatsuo S. Hamazaki; Shinji Komazaki; Shinji Kamimura; Hitoshi Okochi; Makoto Asashima

In the present study, we demonstrated that the mouse embryonic stem cells were differentiated into ciliated epithelial cells, with characteristics of normal ciliated cells. These cells expressed ciliary marker proteins, such as β‐tubulin IV and hepatocyte nuclear factor‐3/forkhead homolog 4 (HFH‐4), and processed microtubules were arranged in the 9 + 2 structure, which is the same specific alignment observed in normal ciliary microtubules. The cilia of these cells were beating at a frequency of 17–20 Hz. The differentiated embryoid bodies (EBs) containing these ciliated cells expressed respiratory marker genes such as thyroid transcription factor‐1 and surfactant protein‐C. For the induction of ciliated cells, culture of EBs in serum‐free medium during the initial 2 days of the attachment was indispensable. When EBs were treated with bone morphogenetic proteins, the expression of HFH‐4 was decreased, and the ciliated cells were scarcely differentiated. Previous methods for inducing ciliated cells in vitro from embryonic or adult tissues involved an air‐liquid interface. The system used in this study more closely mimics the normal development of ciliated cells; thus, an added advantage of the system is as a tool for studying the differentiation mechanism of normal ciliated epithelial cells.


Molecular and Cellular Biology | 2004

ASK1 Inhibits Astroglial Development via p38 Mitogen-Activated Protein Kinase and Promotes Neuronal Differentiation in Adult Hippocampus-Derived Progenitor Cells

Roland Faigle; Anke Brederlau; Muna Elmi; Yvonne Arvidsson; Tatsuo S. Hamazaki; Hidetaka Uramoto; Keiko Funa

ABSTRACT The mechanisms controlling differentiation and lineage specification of neural stem cells are still poorly understood, and many of the molecules involved in this process and their specific functions are yet unknown. We investigated the effect of apoptosis signal-regulating kinase 1 (ASK1) on neural stem cells by infecting adult hippocampus-derived rat progenitors with an adenovirus encoding the constitutively active form of ASK1. Following ASK1 overexpression, a significantly larger number of cells differentiated into neurons and a substantial increase in Mash1 transcription was observed. Moreover, a marked depletion of glial cells was observed, persisting even after additional treatment of ASK1-infected cultures with potent glia inducers such as leukemia inhibitory factor and bone morphogenetic protein. Analysis of the promoter for glial fibrillary acidic protein revealed that ASK1 acts as a potent inhibitor of glial-specific gene transcription. However, the signal transducers and activators of transcription 3 (STAT3)-binding site in the promoter was dispensable, while the activation of p38 mitogen-activated protein kinase was crucial for this effect, suggesting the presence of a novel mechanism for the inhibition of glial differentiation.


Journal of Diabetes Investigation | 2015

Establishment of maturity-onset diabetes of the young-induced pluripotent stem cells from a Japanese patient

Shigeharu Yabe; Naoko Iwasaki; Kazuki Yasuda; Tatsuo S. Hamazaki; Masamitsu Konno; Satsuki Fukuda; Fujie Takeda; Masato Kasuga; Hitoshi Okochi

Maturity‐onset diabetes of the young (MODY) is a heterozygous monogenic diabetes; more than 13 disease genes have been identified. However, the pathogenesis of MODY is not fully understood, because the pancreatic β‐cells of the patients are inaccessable. Therefore, we attempted to establish MODY patient‐derived induced pluripotent stem cells (MODY‐iPS) cells to investigate the pathogenic mechanism of MODY by inducing pancreatic β‐cells. We established MODY5‐iPS cells from a Japanese patient with MODY5 (R177X), and confirmed that MODY5‐iPS cells possessed the characteristics of pluripotent stem cells. In the course of differentiation from MODY5‐iPS cells into pancreatic β‐cells, we examined the disease gene, HNF1B messenger ribonucleic acid. We found that the amount of R177X mutant transcripts was much less than that of wild ones, but they increased after adding cycloheximide to the medium. These results suggest that these R177X mutant messenger ribonucleic acids are disrupted by nonsense‐mediated messenger ribonucleic acid decay in MODY‐iPS cells during the developmental stages of pancreatic β‐cells.


Journal of Dermatological Science | 2015

Synergistic effect of PDGF and FGF2 for cell proliferation and hair inductive activity in murine vibrissal dermal papilla in vitro

Masahiro Kiso; Tatsuo S. Hamazaki; Munenari Itoh; Sota Kikuchi; Hidemi Nakagawa; Hitoshi Okochi

BACKGROUND The dermal papilla is composed of a small clump of mesenchymal cells, called dermal papilla cells (DPCs). DPCs closely interact with epidermal cells to give rise to hair follicles and shafts during hair follicle development and the hair cycle. DPCs are promising cell sources for hair regeneration therapy for alopecia patients. However, once DPCs are put into conventional two-dimensional culture conditions, they quickly lose their capability to produce hair follicles. OBJECTIVE We aimed to expand a sufficiently large population of DPCs that retain their hair inductive activity. METHODS Murine DPCs were cultured in the presence of platelet-derived growth factor-AA (PDGF-AA) and fibroblast growth factor 2 (FGF2). Expressions of follicular-related genes were analyzed by real time PCR and hair inductive activity was determined by patch assay and chamber assay in vivo. RESULTS FGF2 significantly increased the expression of platelet-derived growth factor receptor alpha (PDGFRα) in cultured vibrissal DPCs. PDGF-AA, a ligand of PDGFRα, promoted proliferation of DPCs synergistically when utilized with FGF2 and enhanced the expression of several follicular-related genes in DPCs. Hair reconstitution assays revealed that DPCs treated with both PDGF-AA and FGF-2 were able to maintain their hair inductive activity better than those treated with FGF2 alone. CONCLUSION Both cell proliferation and hair inductive activity in murine DPCs are maintained by the synergistic effect of FGF2 and PDGF-AA.


Journal of Dermatological Science | 2014

Cilostazol improves lymphatic function by inducing proliferation and stabilization of lymphatic endothelial cells

Takayuki Kimura; Tatsuo S. Hamazaki; Makoto Sugaya; Shoji Fukuda; Techuan Chan; Miwa Tamura-Nakano; Shinichi Sato; Hitoshi Okochi

BACKGROUND Cilostazol, an inhibitor of phosphodiesterase type III, is an antiplatelet agent and vasodilator. Some clinical reports have suggested that this drug can improve progressive and refractory lymphedema. OBJECTIVE In this study, we investigated whether cilostazol has the potential to proliferate lymphatic vessels and to improve lymphatic function using human lymphatic endothelial cells (LECs) and mouse lymphedema models. METHODS Human LECs were counted at several time points while they were cultured in the presence of cilostazol and/or protein kinase A inhibitor. After receiving a diet including 0.1% cilostazol or control diet, skin tissue and lymphatic function of k-cyclin transgenic (kCYC(+/-)) mice, which have pernicious lymphatic dysfunction, was analyzed. A different lymphedema model was generated in wild type mice by excising circumferential tail skin to remove the superficial lymphatics. After oral administration of cilostazol, tail lymphedema was examined in this mouse model. RESULTS Proliferation of LECs was promoted in a dose-dependent manner, which was partially inhibited by a protein kinase A inhibitor. Lymphatic vessel count increased in the cilostazol-treated kCYC(+/-) mice over that in the non-treated mice. Lymph flow improved in cilostazol-fed kCYC(+/-) mice as assessed by subcutaneous injection of Evans blue dye into the footpad. Oral administration of cilostazol also decreased lymphedema in a tail of wild type mice. CONCLUSION Cilostazol promoted growth of human LECs and improved lymph flow and lymphedema in two different mouse lymphedema models. These results suggest that cilostazol would be a promising agent for the treatment of lymphedema.


Journal of Biotechnology | 2011

Intracellular reactivation of transcription factors fused with protein transduction domain.

Masamitsu Konno; Shinji Masui; Tatsuo S. Hamazaki; Hitoshi Okochi

Induction of a desired cell type by defined transcription factors (TFs) using iPS technology can be used for cell replacement therapy. However, to overcome problems such as tumor formation, genomic insertional mutagenesis by viral transduction in the induction process needs to be avoided using alternative approaches. One approach could be the direct delivery of TF protein by a protein transduction system, whereby a protein transduction domain (PTD) is fused to facilitate the penetration of cell membrane. However, fusion proteins, including TFs, are reported to be biologically less active through the interference of PTD with proper protein folding. Here, we report a proof-of-concept study in which TF proteins fused with PTDs could be reactivated by removal of PTDs from cells. We demonstrated that Sox2 and Oct3/4 proteins fused with PTD were less active in mouse embryonic stem cells. Removal of PTD by a site-specific protease, derived from tobacco etch virus (TEV), substantially restored the functionality of these proteins, proved by enhanced rescue ability for differentiation induced by endogenous Sox2 and Oct3/4 repression. These results suggest that, by removing a PTD inside the cells, directly delivered TF proteins may exert substantially enhanced function than presently considered.


Journal of Stem Cell Research & Therapy | 2014

Murine Insulinoma Cell-Conditioned Medium with ÃÂETA2/Neurod1 Transduction Efficiently Induces the Differentiation of Adipose-DerivedMesenchymal Stem Cells into ò-Like Cells both In Vitro and In Vivo

Koichi Kawamoto; Shigeharu Yabe; Masamitsu Konno; Hideshi Ishii; Naohiro Nishida; Jun Koseki; Satsuki Fukuda; Yoshito Tomimaru; Naoki Hama; Hiroshi Wada; Shogo Kobayashi; Hidetoshi Eguchi; Masahiro Tanemura; Toshinori Ito; Eun Young Lee; Eri Mukai; Takashi Miki; Yuichiro Doki; Masaki Mori; Tatsuo S. Hamazaki; Hiroaki Nagano; Hitoshi Okochi

Background: Mesenchymal stem cells (MSCs), including adipose tissue-derived mesenchymal stem cells (ADSCs), are multipotent and can differentiate into various cell types, including pancreatic β cells. Therefore, ADSCs present a potential cell source for the treatment of type 1 diabetes mellitus (T1DM). However, current in vitro protocols are insufficient to induce fully matured insulin-producing β cells. In this study, we assessed the effectiveness of overexpression of ΒETA2 (NeuroD1), a member of the basic helix–loop–helix transcription factor family, with murine insulinoma cell line-derived conditioned medium (MIN6-CM) to improve the differentiation capacity of ADSCs into insulin-producing cells. Method: Murine ADSCs were isolated from C57BL/6 mice, transduced with several transcriptional factors (TFs), and stable transfectants were established. MIN6-CM was prepared. Syngeneic recipient mice were rendered diabetic by a single injection of streptozotocin, and differentiated cells were transplanted under the kidney capsule of recipient mice. Next, blood glucose levels were monitored. Results: CM alone was sufficient to induce insulin mRNA expression in vitro. However, other TFs were not detected. ADSCs cultured with MIN6-CM induced insulin expressions in vitro, but other β cell-related TFs were been detected. However, BETA2 transduction in MIN6-CM resulted in robust expression of multiple β cell phenotypic markers. Moreover, insulin content analysis revealed insulin protein expression in vitro. Furthermore, in vivo transplant studies revealed the effectiveness of the simultaneous use of BETA2 transduction with the CM. Conclusion: These results suggest that the balance of cytokines and growth factors in addition to gene manipulation would benefit the efficient differentiation of ADSCs into pancreatic β cells. Our technology could provide a path to β cell differentiation and novel cell replacement-based therapies for T1DM.

Collaboration


Dive into the Tatsuo S. Hamazaki's collaboration.

Top Co-Authors

Avatar
Top Co-Authors

Avatar

Makoto Asashima

National Institute of Advanced Industrial Science and Technology

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Akira Kurisaki

National Institute of Advanced Industrial Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Hiroyuki Kagechika

Tokyo Medical and Dental University

View shared research outputs
Top Co-Authors

Avatar

Kazuki Yasuda

Jichi Medical University

View shared research outputs
Top Co-Authors

Avatar

Kiyoshi Ohnuma

Nagaoka University of Technology

View shared research outputs
Top Co-Authors

Avatar

Koichi Shudo

Tokyo Medical and Dental University

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Shigeharu Yabe

Yokohama City University

View shared research outputs
Researchain Logo
Decentralizing Knowledge