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cell transplantation yagi hiroshi

Sonoko Hasegawa, Hiroaki Kobayashi, Makiko Kumagai, Hiroshi Nishimaru, Etsuko Tarusawa, Hiro Kanda, Makoto Sanbo, Yumiko Yoshimura, Masumi Hirabayashi, Takahiro Hirabayashi, Takeshi Yagi
Neuronal identity is generated by the cell-surface expression of clustered protocadherin (Pcdh) isoforms. In mice, 58 isoforms from three gene clusters, Pcdhα, Pcdhβ, and Pcdhγ, are differentially expressed in neurons. Since cis-heteromeric Pcdh oligomers on the cell surface interact homophilically with that in other neurons in trans, it has been thought that the Pcdh isoform repertoire determines the binding specificity of synapses. We previously described the cooperative functions of isoforms from all three Pcdh gene clusters in neuronal survival and synapse formation in the spinal cord...
2017: Frontiers in Molecular Neuroscience
Yoshihiro Ono, Angelica Pérez-Gutiérrez, Mladen I Yovchev, Kentaro Matsubara, Shinichiro Yokota, Jorge Guzman-Lepe, Kan Handa, Alexandra Collin de l'Hortet, Angus W Thomson, David A Geller, Hiroshi Yagi, Michael Oertel, Alejandro Soto-Gutierrez
BACKGROUND: Auxiliary partial liver transplantation (APLT) in humans is a therapeutic modality used especially to treat liver failure in children or congenital metabolic disease. Animal models of APLT have helped to explore therapeutic options. Though many groups have suggested improvements, standardizing the surgical procedure has been challenging. Additionally, the question of whether graft livers are reconstituted by recipient-derived cells after transplantation has been controversial...
January 2017: Transplantation
Hiroto Kitahara, Hiroshi Yagi, Kazuki Tajima, Kazuma Okamoto, Akihiro Yoshitake, Ryo Aeba, Mikihiko Kudo, Ichiro Kashima, Shinji Kawaguchi, Akinori Hirano, Mio Kasai, Yuta Akamatsu, Hidetoshi Oka, Yuko Kitagawa, Hideyuki Shimizu
OBJECTIVES: One of the final treatments for end-stage heart failure is heart transplantation. However, a shortage of donor hearts has created a long waiting list and limited benefits. Our ultimate goal is to create a whole beating heart fabricated on an organ scaffold for human heart transplantation. Here, we successfully performed the first transplantation using a decellularized whole porcine heart with mesenchymal stem cells. METHODS: A porcine heart was harvested following cardiac arrest induced by a high-potassium solution and stored at -80°C for 24 h...
May 2016: Interactive Cardiovascular and Thoracic Surgery
A Collin de l'Hortet, K Takeishi, J Guzman-Lepe, K Handa, K Matsubara, K Fukumitsu, K Dorko, S C Presnell, H Yagi, A Soto-Gutierrez
Liver transplantation, either a partial liver from a living or deceased donor or a whole liver from a deceased donor, is the only curative therapy for severe end-stage liver disease. Only one-third of those on the liver transplant waiting list will be transplanted, and the demand for livers is projected to increase 23% in the next 20 years. Consequently, organ availability is an absolute constraint on the number of liver transplants that can be performed. Regenerative therapies aim to enhance liver tissue repair and regeneration by any means available (cell repopulation, tissue engineering, biomaterials, proteins, small molecules, and genes)...
June 2016: American Journal of Transplantation
Kazuko Koike, Akinobu Takaki, Takahito Yagi, Yoshiaki Iwasaki, Tetsuya Yasunaka, Hiroshi Sadamori, Susumu Shinoura, Yuzo Umeda, Ryuichi Yoshida, Daisuke Sato, Daisuke Nobuoka, Masashi Utsumi, Yasuhiro Miyake, Fusao Ikeda, Hidenori Shiraha, Toshiyoshi Fujiwara, Kazuhide Yamamoto
BACKGROUND: Post orthotopic liver transplantation (OLT) viral hepatitis is an immunological condition where immune cells induce hepatitis during conditions of immune-suppression. The immune-regulatory programmed death-1 (PD-1)/PD-ligand 1 system is acknowledged to play important roles in immune-mediated diseases. However, the PD-1/PD-L2 interaction is not well characterized, with PD-L2 also exhibiting an immunostimulatory function. We hypothesized that this atypical molecule could affect the recurrence of post-OLT hepatitis...
July 2015: Transplantation
Ryuichiro Tsuzaki, Akinobu Takaki, Takahito Yagi, Fusao Ikeda, Kazuko Koike, Yoshiaki Iwasaki, Hidenori Shiraha, Yasuhiro Miyake, Hiroshi Sadamori, Susumu Shinoura, Yuzo Umeda, Ryuichi Yoshida, Daisuke Nobuoka, Masashi Utsumi, Eiichi Nakayama, Toshiyoshi Fujiwara, Kazuhide Yamamoto
It is not known how the immune system targets hepatitis C virus (HCV)-infected HLA-mismatched hepatocytes under immune-suppressed conditions after orthotopic liver transplantation (OLT). In addition, the relationship between the HCV-specific immune response and IL28B variants as predictors of HCV clearance has not been well-characterized. We determined the IL28B polymorphisms for 57 post-OLT HCV carriers, and we assessed the HCV-specific immune responses by measuring the peripheral blood mononuclear cell-derived HCV-specific interferon-gamma (IFN-γ) response using an enzyme-linked immunospot assay...
2014: Acta Medica Okayama
Masashi Utsumi, Akinobu Takaki, Yuzo Umeda, Kazuko Koike, Stephanie C Napier, Nobukazu Watanabe, Hiroshi Sadamori, Susumu Shinoura, Ryuichi Yoshida, Daisuke Nobuoka, Tetsuya Yasunaka, Eiichi Nakayama, Kazuhide Yamamoto, Toshiyoshi Fujiwara, Takahito Yagi
INTRODUCTION: Regulatory T (Treg) and type 1 regulatory T (Tr1) cells facilitate hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT). However, their frequencies and effects on HCV-specific immune responses have not been well investigated. METHODS: We determined Treg and Tr1 frequencies in OLT patients with hepatitis C and assessed their associations with HCV-specific T cell responses. These patients comprised the following groups: an early post-transplantation group (n=14); an OLT-chronic active hepatitis C group (n=14) with active hepatitis C (alanine aminotransferase of>upper limit of normal/positive for HCV-RNA); an OLT-persistently normal alanine aminotransferase group (n=12) without active hepatitis C (not interferon/positive for HCV-RNA); and an OLT-sustained viral response group (n=6) with sustained viral responses using interferon treatment (negative for HCV-RNA)...
June 2014: Transplant Immunology
Hiroto Kikuchi, Hiroshi Yagi, Hirotoshi Hasegawa, Yoshiyuki Ishii, Koji Okabayashi, Masashi Tsuruta, Go Hoshino, Atsushi Takayanagi, Yuko Kitagawa
BACKGROUND: Mesenchymal stem cells (MSCs) are being developed as a new clinically relevant stem cell type to be recruited into and to repair injured tissue. A number of studies have focused on the therapeutic potential of MSCs by virtue of their immunomodulatory properties. Systemically administered MSCs can also migrate to sites of malignancies. Because of this latter phenomenon, we transfected human MSCs to secrete anti-high mobility group box (HMGB) 1 proteins. They were then injected into mice bearing human colon cancer to evaluate their efficacy as an antineoplastic agent...
July 2014: Journal of Surgical Research
Yoshie Kadota, Hiroshi Yagi, Kenta Inomata, Kentaro Matsubara, Taizo Hibi, Yuta Abe, Minoru Kitago, Masahiro Shinoda, Hideaki Obara, Osamu Itano, Yuko Kitagawa
Recent studies suggest that organ decellularization is a promising approach to facilitate the clinical application of regenerative therapy by providing a platform for organ engineering. This unique strategy uses native matrices to act as a reservoir for the functional cells which may show therapeutic potential when implanted into the body. Appropriate cell sources for artificial livers have been debated for some time. The desired cell type in artificial livers is primary hepatocytes, but in addition, other supportive cells may facilitate this stem cell technology...
April 2014: Organogenesis
Hiroshi Yagi, Alejandro Soto-Gutierrez, Yuko Kitagawa
Recovery from end-stage organ failure presents a challenge for the medical community, considering the limitations of extracorporeal assist devices and the shortage of donors when organ replacement is needed. There is a need for new methods to promote recovery from organ failure and regenerative medicine is an option that should be considered. Recent progress in the field of tissue engineering has opened avenues for potential clinical applications, including the use of microfluidic devices for diagnostic purposes, and bioreactors or cell/tissue-based therapies for transplantation...
June 2013: Surgery Today
Hiroshi Yagi, Yuko Kitagawa
New methods to facilitate recovery from end-stage organ failure are needed since only limited treatment options are available in this context, including replacement therapy such as hemodialysis or organ transplantation. Recent progress in the field of tissue engineering has opened attractive approaches for clinical applications of regenerative medicine which could be an option in this regard. Of these, tissue decellularization technology, which retains all the necessary cues for cell maintenance and homeostasis, such as the three-dimensional structure of the organ and its extracellular matrix components, has recently been applied to whole organs...
September 2012: Nihon Geka Gakkai Zasshi
Junya Matsumi, Hiroshi Morimatsu, Takashi Matsusaki, Ryuji Kaku, Hiroko Shimizu, Toru Takahashi, Takahito Yagi, Masaki Matsumi, Kiyoshi Morita
Living donor liver transplantation (LDLT) requires ischemia/reperfusion (I/R), which can cause early graft injury. However, the detailed mechanism of I/R injury remains unknown. Heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme catabolism and results in the production of iron, carbon monoxide (CO), and biliverdin IXα. Furthermore, in animals, HO-1 has a protective effect against oxidative stress associated with I/R injury. However, in humans, the molecular mechanism and clinical significance of HO-1 remain unclear...
February 2012: International Journal of Molecular Medicine
Kazumasa Fukuda, Yoshiro Saikawa, Hiroshi Yagi, Norihito Wada, Tsunehiro Takahashi, Yuko Kitagawa
The interaction between gastric cancer (GC) cells and the peritoneum is a critical event in peritoneal dissemination. The molecular mechanisms of this dissemination, however, remain unclear. Integrins are heterodimeric cell adhesion molecules consisting of α and β subunits that serve as adhesion receptors for extracellular matrix proteins and cellular ligands, and may participate in GC peritoneal dissemination. In this study, we isolated fresh GC cells from a patient with peritoneal metastasis and examined them for integrin expression and investigated the role of integrin α1 subunit molecules in GC...
February 2012: Molecular Medicine Reports
Hiroshi Yagi, Wenfu Tan, Patricia Dillenburg-Pilla, Sylvain Armando, Panomwat Amornphimoltham, May Simaan, Roberto Weigert, Alfredo A Molinolo, Michel Bouvier, J Silvio Gutkind
Tumor cells can co-opt the promigratory activity of chemokines and their cognate G protein-coupled receptors (GPCRs) to metastasize to regional lymph nodes or distant organs. Indeed, the migration toward SDF-1 (stromal cell-derived factor 1) of tumor cells bearing CXCR4 [chemokine (C-X-C motif) receptor 4] has been implicated in the lymphatic and organ-specific metastasis of various human malignancies. Here, we used chimeric G proteins and GPCRs activated solely by artificial ligands to selectively activate the signaling pathways downstream of specific G proteins and showed that CXCR4-mediated chemotaxis and transendothelial migration of metastatic basal-like breast cancer cells required activation of Gα(13), a member of the Gα(12/13) G protein family, and of the small guanosine triphosphatase Rho...
September 20, 2011: Science Signaling
Yoshifumi Matsuura, Hiroshi Yagi, Sachiko Matsuda, Osamu Itano, Koichi Aiura, Shun'ichi Kuroda, Masakazu Ueda, Yuko Kitagawa
For the targeted delivery of genes and drugs to the human liver, hepatitis B virus (HBV) envelope L particles, which form hollow nanoparticles and display a peptide that is indispensable for liver-specific infection by HBV in humans, should be a useful tool. To test the efficacy of these particles in vivo, in the present study we generated a small animal model harboring a functional human liver tissue xenograft. An anti-asialo GM1 antibody was administered to SCID mice to induce the depletion of natural-killer-cell-dependent immune responsibility and then the mice underwent transplantation of a noncancerous liver tissue originating in humans into the kidney capsule...
2011: European Surgical Research. Europäische Chirurgische Forschung. Recherches Chirurgicales Européennes
Hiroshi Yagi, Alejandro Soto-Gutierrez, Nalu Navarro-Alvarez, Yaakov Nahmias, Yoni Goldwasser, Yuko Kitagawa, Arno W Tilles, Ronald G Tompkins, Biju Parekkadan, Martin L Yarmush
Excessive systemic inflammation following trauma, sepsis, or burn could lead to distant organ damage. The transplantation of bone marrow stromal cells or mesenchymal stem cells (MSCs) has been reported to be an effective treatment for several immune disorders by modulating the inflammatory response to injury. We hypothesized that MSCs can dynamically secrete systemic factors that can neutralize the activity of inflammatory cytokines. In this study, we showed that cocultured MSCs are able to decrease nuclear factor κ-B (NFκB) activation in target epithelial cells incubated in inflammatory serum conditions...
October 2010: Molecular Therapy: the Journal of the American Society of Gene Therapy
Hiroshi Yagi, Alejandro Soto-Gutierrez, Yuko Kitagawa, Arno W Tilles, Ronald G Tompkins, Martin L Yarmush
Bone marrow mesenchymal stromal cells (MSCs) suppress immune cell responses and have beneficial effects in various inflammatory-related immune disorders. A therapeutic modality for systemic inflammation and its consequences is not available yet. Thus, this work investigates the therapeutic effects of MSCs in injury models induced by lipopolysaccharide (LPS) or burn. Gene expression was analyzed in MSCs when exposed to inflammatory serum from injured animals and it showed remarkable alterations compared to normal culture...
2010: Cell Transplantation
Alejandro Soto-Gutierrez, Nalú Navarro-Alvarez, Hiroshi Yagi, Yakoov Nahmias, Martin L Yarmush, Naoya Kobayashi
Cell-based technologies to support/restore liver function represent one of the most promising opportunities in the treatment of acute liver failure. However, the understanding of the constituent cell types that interact to achieve liver-specific structure and function has not been achieved in the development of liver assist devices (LADs). Here we show that hepatocytes migrated toward and adhered and formed sinusoids-like structures in conjunction with liver nonparenchymal cells, and that this liver organoid formed sophisticated tissue after 7 days in an implanted LAD in rodents...
2010: Cell Transplantation
Hideo Kohka Takahashi, Jiyong Zhang, Shuji Mori, Keyue Liu, Hidenori Wake, Rui Liu, Hiroshi Sadamori, Hiroaki Matsuda, Takahito Yagi, Tadashi Yoshino, Masahiro Nishibori
Posttransplant diabetes mellitus is a frequent complication among transplant recipients. Ligation of advanced glycation end products (AGEs) with their receptor on monocytes/macrophages plays a role in diabetes complications. The enhancement of adhesion molecule expression on monocytes/macrophages activates T cells, reducing allograft survival. In previous work, we found that toxic AGEs, AGE-2 and AGE-3, induced the expression of intracellular adhesion molecule-1, B7.1, B7.2, and CD40 on monocytes, production of interferon-gamma and tumor necrosis factor alpha, and lymphocyte proliferation during human mixed lymphocyte reaction...
September 1, 2010: Journal of Pharmacology and Experimental Therapeutics
Hiroshi Yagi, Alejandro Soto-Gutierrez, Biju Parekkadan, Yuko Kitagawa, Ronald G Tompkins, Naoya Kobayashi, Martin L Yarmush
Mesenchymal stem cell (MSC) transplantation has been explored as a new clinical approach to repair injured tissue. A growing corpus of studies have highlighted two important aspects of MSC therapy: 1) MSCs can modulate T-cell-mediated immunological responses, and (2) systemically administered MSCs home to sites of ischemia or injury. In this review, we describe the known mechanisms of immunomodulation and homing of MSCs. First, we examine the low immunogenicity of MSCs and their antigen presentation capabilities...
2010: Cell Transplantation
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