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Laboratory of Disease Control
Ageyama group
Ageyama Naohide >> 
Outline of research
In our group, use of nonhuman primates as models to study, prevent and/or treat human diseases under the animal welfare. Among large animals, nonhuman primates may provide the best models because of their close phylogenetic relationship to humans. Especialy, macaque monkeys are important with regard to extrapolation into humans in the medical field. One of the missions of our group is to engage in basic and applied, collaborative and contract research in association with academia and industry.

1. Hematopoietic stem cell transplantation for gene and cell therapy.

Hematopietic stem cells are widely used for autologous and allogeneic transplantation therapies to treat hematological malignancies such as leukemia and lymphoma. The cells have also been intensively studied as a donor source of stem cells for gene and cell therapies. Autologous transplantation models are ideal for evaluating engraftment, proliferation, and differentiation of HSCs, since natural hematopoiesis can be studied in these models. Although mouse transplantation models have been widely used for assay of murine HSCs, these models may not reliably predict the biology of HSCs in larger animals such as humans. A typical mouse makes, in a two-year lifetime, the same amount of red blood cells as does man in one day, raising the possibility that HSCs kinetics in large animals are more complex. As these results, we can easily imagine that dynamics and control of HSCs make a difference in human and mice. We established safe and efficient methods for collection of hematopietic stem cells and autologous transplantation of hematopoietic stem cells in nonhuman primates. Our nonhuman primate model will provide an important framework for such future clinical studies. In fact, we achieved successful evaluation as a preclinical gene therapy and cell therapy using this model.

2. Cardiovascular disease

Cardiovascular disease is the most common cause of death among the elderly, and cardiovascular deaths increase significantly developed countries. These causes are not yet clear whether aging acts synergistically to intensify cardiovascular disease. It is important to develop the new therapies for cardiovascular diseases and elucidate the pathophysiology of cardiovascular diseases. The close phylogenetic relationship of macaque monkeys to humans has resulted in their widespread use as a preclinical model for cardiac disease such as ischemic myocardium. However, there have been very few reported cases of cardiac diseases in monkeys definitely antemortem diagnosis. So, we trying to establish the monkey models for cardiac diseases underwent a thorough examination of the circulatory organs by the noninvasive methods that electrocardiography, radiography, echocardiography, blood pressure, magnetic resonance imaging and blood chemistry test. We extracted the monkey cardiac diseases that ventricular septal defects, double chambered right ventricle, valvular diseases, endocarditis and cardiomyopathy from cynomolgus breeding colony. If these monkey diseases will be establish the model for cardiovascular diseases, it may be continue to offer unique insights into the biology of cardiology.
Publication
2005
  1. Ageyama N, Hanazono Y, Shibata H, Ono F, Nagashima T, Ueda Y, Yoshikawa Y, Hasegawa M, Ozawa K, Terao K.
    Prevention of Immune Responses to Human Erythropoietin in Cynomolgus Monkeys (Macaca fascicularis).
    J Vet Med Sci., In press.
  2. Ageyama N, Hanazono Y, Shibata H, Ono F, Ogawa H, Nagashima T, Ueda Y, Yoshikawa Y, Hasegawa M, Ozawa K, Terao K.
    Safe And Efficient Collection of Cytokine-Mobilized Peripheral Blood Cells From Cynomolgus Monkeys (Macaca fascicularis) with Human Newborn-Equivalent Body Weights.
    Exp Anim., 2005; 54:421-428.
  3. Koie H, Ageyama N, Ono F, Kanayama k, Sakai T, Sankai T.
    Antemortem diagnosis with muscular interventricular septal defect in a cynomolgus monkey (Macaca fascicularis).
    Contemp Top Lab Anim Sci., 2005; 44:26-28.
  4. Hara M, Kikuchi T, Ono F, Takano J, Ageyama N, Fujimoto K, Terao K, Baba T, Mukai R.
    Survey of Captive Cynomolgus Macaque Colonies for SRV/D Infection Using Polymerase Chain Reaction Assays.
    Comp Med., 2005;55:145-149.
  5. Yoshioka T, Ageyama N, Shibata H, Yasu T, Misawa Y, Takeuchi K, Matsui K, Yamamoto K, Terao K, Shimada K, Ikeda U, Ozawa K, Hanazono Y.
    Repair of Infarcted Myocardium Mediated by Transplanted Bone Marrow-Derived CD34+Stem Cells in A Nonhuman Primate Model.
    Stem Cells., 2005;23:355-336.
2004
  1. Ueda K, Hanazono Y, Ageyama N, Shibata H, Ogata S, Ueda Y, Tabata T, Ikehara S, Taniwaki M, Hasegawa M, Terao K, Ozawa K.
    Intra-bone marrow transplantation of hematopoietic stem cells in non-human primates: long-term engraftment without conditioning.
    Gene Therapy and Regulation., 2004;2:207-218
  2. Ueda K, Hanazono Y, Shibata H, Ageyama N, Ueda Y, Ogata S, Tabata T, Nagashima T, Takatoku M, Kume A, Ikehara S, Taniwaki M, Terao K, Hasegawa M, Ozawa K.
    High-Level In Vivo Gene Marking After Gene-Modified Autologous Hematopoietic Stem Cell Transplantation Without Marrow Conditioning in Nonhuman Primates.
    Molcular Therapy., 2004;10:469-477
  3. Sato Y, Koketsu D, Ageyama N, Ono F, Miyamoto Y, Hisatsune T.
    Successful Retrograde Transport of Fluorescent Latex Nanospheres in the Cerebral Cortex of the Macaque Monkey.
    Exp Anim., 2004;53:383-386
  4. Nagashima T, Ueda Y, Hanazono Y, Kume A, Shibata H, Ageyama N, Terao K, Ozawa K, Hasegawa M.
    In vivo expansion of gene-modified hematopoietic cells by a novel selective amplifier gene utilizing the erythropoietin receptor as a molecular switch.
    J Gene Med., 2004;6:22-31
2003
  1. Asano T, Ageyama N, Takeuchi K, Momoeda M, Kitano Y, Sasaki K, Ueda Y, Suzuki Y, Kondo Y, Torii R, Hasegawa M, Ookawara S, Harii K, Terao K, Ozawa K, Hanazono Y.
    Engraftment and tumor formation after allogeneic in utero transplantation of primate embryonic stem cells.
    Transplantation., 2003; 15:1061-1067
  2. Shibta H, HanazonoY, Ageyama N, Nagashima T, Ueda Y, Hasegawa M, Ozawa K, Yoshikawa Y, Terao K.
    Collection and analysis of hematopoietic progenitor cells from cynomolgus macaques (Macaca fascicularis): Assessment of cross-reacting monoclonal antibodies.
    Am J Primatol., 2003; 61:3-123.       
  3. Ageyama N, Kimikawa M, Eguchi K, Ono F, Shibata H, Yoshikawa Y, Terao K.
    Modification of the Leukapheresis Procedure for Use in Rhesus Monkeys (Macaca mulata).
    J Clin Apher., 2003;18:26-31
  4. Nagashima T, Ueda Y, Hanazono Y, Kume A, Shibata H, Ageyama N, Terao K, Ozawa K, Hasegawa M.
    New selective amplifier genes containing c-Mpl for hematopoietic cell expansion.
    Biochem Biophys Res Commun., 2003;303:170-176
2002
  1. Ageyama N, Hanazono Y, Shibata H, Ohto K, Ono F, Nagashima T, Ueda Y, Donahue R, Hasegawa M, Ozawa K, Yoshikawa Y, Terao K.
    Safe and Efficient Methods of Autologous Hematopoietic Stem Cell Transplantation for Biomedical Research in Cynomolgus Monkeys.
    Comp Med., 2002;52:445-451
  2. Hanazono Y, Terao K, Shibata H, Nagashima T, Ageyama N, Asano T, Ueda Y, Kato I, Kume A, Hasegawa M, Ozawa K.
    Introduction of the green fluorescent protein gene into hematopoietic stem cells results in prolonged discrepancy of in vivo transduction levels between bone marrow progenitors and peripheral blood cells in nonhuman primates.
    J Gene Med., 2002;4:470-477
  3. Hanazono Y, Nagashima T, Takatoku M, Shibata H, Ageyama N, Asano T, Ueda Y, Dunbar CE, Kume A, Terao K, Hasegawa M, Ozawa K.
    In vivo selective expansion of gene-modified hematopoietic cells in a nonhuman primate model.
    Gene Ther., 2002;9:1055-1064
2001
  1. Ageyama N, Shibata H, Narita H, Hanari K, Kohno A, Ono F, Yoshikawa Y, Terao K. Specific gravity of whole blood in cynomolgus monkeys (Macaca fascicularis), squirrel monkeys (Saimiri sciureus) and tamarins (Saguinus labiatus) and total blood volume in cynomolgus monkeys. Contemp Top Lab Anim Sci., 2001;40:33-35
2000
  1. Kushida T, Inaba M, Ikebukuro K, Ngahama T, Oyaizu H, Lee S, Ito T, Ichioka N, Hisha H, Sugiura K, Miyashima S, Ageyama N, Ono F, Iida H, Ogawa R, Ikehara S.
    A New Method for Bone Marrow Cell Harvesting.
    Stem Cells., 2000;18:453-456
Contact

Tsukuba Primate Research Center,
National Institute of Biomedical Innovation,
Hachimandai 1, Tsukuba, Ibaraki, 305-0843 Japan
E-mail  
Tel  +81-29-837-2121
Fax  +81-29-837-0218