Basic Research in Cardiology

, Volume 105, Issue 3, pp 409–417

Mesenchymal stem cell-based prostacyclin synthase gene therapy for pulmonary hypertension rats

  • Kiyoko Takemiya
  • Hisashi Kai
  • Hideo Yasukawa
  • Nobuhiro Tahara
  • Seiya Kato
  • Tsutomu Imaizumi
Original Contribution

DOI: 10.1007/s00395-009-0065-8

Cite this article as:
Takemiya, K., Kai, H., Yasukawa, H. et al. Basic Res Cardiol (2010) 105: 409. doi:10.1007/s00395-009-0065-8

Abstract

Mesenchymal stem cells (MSCs) are the pluripotent cells, which enter the circulation and home to sites of tissue injury or inflammation. MSCs are highlighted as a potential cell vector for gene therapy. In this study, we investigated whether transplanted allogeneic MSCs preferentially accumulate in the lung in rats with pulmonary hypertension (PH) and if so to determine the efficacy of MSC-based prostacyclin synthase (PCS) gene therapy for PH. PH was induced in Lewis rats by injecting monocrotaline at 7-weeks-old (week 0). MSCs were obtained by culturing bone marrow mononuclear cells. Allogeneic MSCs were intravenously transplanted at week 2 when moderate PH had been established. PH enhanced indium-111-oxine-labeled MSC accumulation in the lungs, but not in other organs, 2.5-times and 6-times, 1 and 14 days after transplantation, respectively. Transplantation of MSCs transduced with PCS (PSC-MSCs), but not with GFP (GFP-MSCs), reduced PH, pulmonary arterial thickening, and RV hypertrophy at week 4. The lung prostacyclin production was impaired in PH rats, which was restored and maintained for long time by PCS-MSCs, but not by GFP-MSCs. The survival rate at week 7 was 100% in PCS-MSC-transplanted PH rats, whereas they were 38 and 44% in PH rats and GFP-MSC-transplanted PH rats, respectively. In conclusion, the gene-engineered MSCs would be a suitable cell vector for gene delivery specifically to the PH lung. The allogeneic PCS-MSC transplantation attenuated PH and cardiovascular remodeling, and improved the prognosis in PH rats. The MSC-based PCS gene therapy may be a promising strategy for PH treatment.

Keywords

Mesenchymal stem cell Pulmonary hypertension Gene therapy 

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Kiyoko Takemiya
    • 1
  • Hisashi Kai
    • 1
  • Hideo Yasukawa
    • 1
    • 2
  • Nobuhiro Tahara
    • 1
  • Seiya Kato
    • 1
    • 3
  • Tsutomu Imaizumi
    • 1
  1. 1.Department of Internal Medicine Division of Cardio-Vascular MedicineKurume University School of MedicineKurumeJapan
  2. 2.Cardiovascular Research InstituteKurume University School of MedicineKurumeJapan
  3. 3.Department of Pathology and Cell Biology, Graduate School and Faculty of MedicineUniversity of RyukyusNishiharaJapan

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