Effects of Transplanted Human Cord Blood-Mononuclear Cells on Pulmonary Hypertension in Immunodeficient Mice and Their Distribution

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  • Sugano Mikio
    Department of Cardiovascular Surgery, Graduate School of Biomedical Sciences, Tokushima University
  • Yoshida Homare
    Department of Cardiovascular Surgery, Graduate School of Biomedical Sciences, Tokushima University
  • Kurobe Hirotsugu
    Department of Cardiovascular Surgery, Graduate School of Biomedical Sciences, Tokushima University
  • Arase Hiroki
    Department of Cardiovascular Surgery, Graduate School of Biomedical Sciences, Tokushima University
  • Kinoshita Hajime
    Department of Cardiovascular Surgery, Graduate School of Biomedical Sciences, Tokushima University
  • Kitaichi Takashi
    Department of Cardiovascular Surgery, Graduate School of Biomedical Sciences, Tokushima University
  • Sugasawa Noriko
    Department of Cardiovascular Surgery, Graduate School of Biomedical Sciences, Tokushima University
  • Nakayama Soichiro
    Department of Gynecology, Graduate School of Biomedical Sciences, Tokushima University
  • Maeda Kazuhisa
    Department of Gynecology, Graduate School of Biomedical Sciences, Tokushima University
  • Irahara Minoru
    Department of Gynecology, Graduate School of Biomedical Sciences, Tokushima University
  • Kitagawa Tetsuya
    Department of Cardiovascular Surgery, Graduate School of Biomedical Sciences, Tokushima University

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<p>Objectives: To investigate the effects of human umbilical cord blood-derived mononuclear cell (hUCB-MNC) transplantation on pulmonary hypertension (PH) induced by monocrotaline (MCT) in immunodeficient mice and their distribution. Methods: MCT was administered to BALB/c Slc-nu/nu mice, and PH was induced in mice 4 weeks later. Fresh hUCB-MNCs harvested from a human donor after her delivery were injected intravenously into those PH mice. The medial thickness of pulmonary arterioles, ratio of right ventricular to septum plus left ventricular weight (RV/S+LV), and ratio of acceleration time to ejection time of pulmonary blood flow waveform (AT/ET) were determined 4 weeks after hUCB-MNC transplantation. To reveal the incorporation into the lung, CMTMR-labeled hUCB-MNCs were observed in the lung by fluorescent microscopy. DiR-labeled hUCB-MNCs were detected in the lung and other organs by bioluminescence images. Results: Medial thickness, RV/S+LV and AT/ET were significantly improved 4 weeks after hUCB-MNC transplantation compared with those in mice without hUCB-MNC transplantation. CMTMR-positive hUCB-MNCs were observed in the lung 3 hours after transplantation. Bioluminescence signals were detected more strongly in the lung than in other organs for 24 hours after transplantation. Conclusions: The results indicate that hUCB-MNCs are incorporated into the lung early after hUCB-MNC transplantation and improve MCT-induced PH. J. Med. Invest. 64: 43-49, February, 2017</p>

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