Allogeneic Transplantation of Fetal Membrane–Derived Mesenchymal Stem Cell Sheets Increases Neovascularization and Improves Cardiac Function after Myocardial Infarction in Rats

Authors:
  • SIShin Ishikane
    Shin Ishikane
  • HHHiroshi Hosoda
    Hiroshi Hosoda
  • KYKenichi Yamahara
    Kenichi Yamahara
  • YAYoshiharu Akitake
    Yoshiharu Akitake
  • JKJung Kyoungsook
    Jung Kyoungsook
  • KMKenichi Mishima
    Kenichi Mishima
  • KIKatsunori Iwasaki
    Katsunori Iwasaki
  • MFMichihiro Fujiwara
    Michihiro Fujiwara
  • MMMikiya Miyazato
    Mikiya Miyazato
  • KKKenji Kangawa
    Kenji Kangawa
  • TITomoaki Ikeda
    Tomoaki Ikeda
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Abstract
Mesenchymal stem cell (MSC) transplantation has been pursued as a new method to repair damaged myocardium. We focused on the fetal membrane (FM) as an alternative source to bone marrow (BM)-derived MSCs. In this study, we investigated whether transplantation of allogeneic FM-MSC sheets could attenuate myocardial dysfunction in a rat chronic myocardial infarction (MI) model. Sheets of allogeneic FM-MSC or autologous BM-MSC were transplanted into the scarred myocardium 4 weeks after coronary ligation. Four weeks after transplantation, both allogeneic FM-MSC and autologous BM-MSC sheets had significantly improved cardiac function and reduced myocardial fibrosis compared with the untreated MI group. In both MSC sheet-transplanted groups, the peri-infarct regional capillary density was increased. Some engrafted MSCs formed vascular structures and were positive for lectin I and α-smooth muscle actin. The numbers of engrafted cells and differentiated cells were very low after both types of MSC sheet transplantation. CD3 T cells did not increase in the transplantation site, but CD163 M2 macrophages increased in the groups transplanted with allogeneic FM-MSC and autologous BM-MSC. Transplantation of allogeneic FM-MSC or autologous BM-MSC sheets attenuated myocardial dysfunction in a rat MI model to a similar degree. The engraftment rate of transplanted cells and immune cell infiltration into the transplanted area did not differ between the two types of MSC transplants. M2 macrophage induction has possible involvement in the therapeutic effects of MSC transplantation. Allogeneic FM-MSC sheet transplantation might be a new therapeutic strategy after MI.

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