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Transplantation of sendai viral angiopoietin-1-modified mesenchymal stem cells for ischemic limb disease

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Abstract

Sendai viral vector (SeV) is emerging as a promising vector for gene therapy. However, little information is available regarding the combination of SeV-mediated gene and mesenchymal stem cell (MSC) therapy in dealing with ischemic diseases. In this study, we infected SeV to the MSCs in vitro; and injected MSCs modified with SeV harboring human angiopoietin-1 gene (SeVhAng-1) into the ischemic limb of rats in vivo. We found SeV had high transductive efficiency to the MSCs. Both MSCs and SeVhAng-1-modified MSCs improved the blood flow recovery and increased the capillary density of the ischemic limb, compared with the control. However, in contrast to MSCs, SeVhAng-1-modified MSCs had a better improvement of blood flow recovery in the ischemic limb. We further found the ischemic limb injected with SeVhAng-1-modified MSCs had strong expression of p-Akt, which improved survival of MSCs injected into the ischemic limb. This indicated SeVhAng-1 modification enhanced angiogenetic effect of MSCs by both angiogenesis and cell protection. We conclude that SeVhAng-1-modified MSCs may serve as a more effective tool in dealing with ischemic limb disease.

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Acknowledgments

This work was partly supported by a grant to HH from the Ministry of Education, Science, Japan and a grant to HJ from National Natural Science Foundation of China [30960379]. We thank Takeo Yamamoto for his technical assistance in vector construction.

Author information

Authors and Affiliations

  1. Department of Laboratory Medicine, Ningxia People’s Hospital, YinChuan, China

    Wenhua Piao

  2. Department of Cardiac Surgery, Shenyang Northern Hospital, ShenYang, China

    Huishan Wang & Jianhua Huang

  3. DNAVEC Research Corporation, Tsukuba, Ibaraki, Japan

    Makoto Inoue & Mamoru Hasegawa

  4. Department of Cardiothoracic Surgery, Ningxia People’s Hospital, 148# HuaiYuan West Road, XiXia District, YinChuan, 750021, China

    Jianhua Huang

  5. Department of Molecular Medicine, Sapporo Medical University, South 1, West 17, Chuo-ku, Sapporo, 060-8556, Japan

    Hirofumi Hamada & Jianhua Huang

Authors
  1. Wenhua Piao
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  2. Huishan Wang
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  3. Makoto Inoue
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  4. Mamoru Hasegawa
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  5. Hirofumi Hamada
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  6. Jianhua Huang
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Corresponding authors

Correspondence to Hirofumi Hamada or Jianhua Huang.

Additional information

Dr. Wenhua Piao and Huishan Wang contributed equally to this work.

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Piao, W., Wang, H., Inoue, M. et al. Transplantation of sendai viral angiopoietin-1-modified mesenchymal stem cells for ischemic limb disease. Angiogenesis 13, 203–210 (2010). https://doi.org/10.1007/s10456-010-9169-x

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  • DOI: https://doi.org/10.1007/s10456-010-9169-x

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