Neovascularization promoted by mononuclear cell transplantation after transient cerebral ischemia in mice

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  • Funabiki Tomohiro
    Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Tokyo, Japan
  • Namiki Jun
    Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Tokyo, Japan
  • Suzuki Sayuri
    Center of Integrated Medical Research, Keio University School of Medicine, Tokyo, Japan
  • Matsuzaki Yumi
    Department of Physiology, Keio University School of Medicine, Tokyo, Japan
  • Aikawa Naoki
    Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Tokyo, Japan

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Abstract

Objectives: Ischemic stroke can cause major disability and a deteriorated quality of life. The purposes of this study were to examine whether neovascularization might be promoted by the intra-arterial transplantation of mononuclear cells (MNCs) in ischemic murine brain and to determine whether the new endothelial cells are derived from the donor or from the recipient.<BR>Methods: Transient middle cerebral artery occlusion was accomplished using the intraluminal filament technique. Immediately after the embolus was withdrawn, MNCs harvested from C57BL/6J mice (wild-MNCs) or transgenic mice ubiquitously expressing green fluorescent protein (EGFP-MNCs) were infused intra-arterially. The brains of the mice were then sectioned and stained with anti-CD31 antibody to detect the endothelial cells.<BR>Results: At 30 minutes after operation, transplanted EGFP-MNCs were found in the lung, spleen, and liver but not in the brain. At 6 weeks after operation, CD31-positive cells were evident in the murine brain transplanted with MNCs. Furthermore, the CD31-positive cells were stained with anti-GFP antibody in EGFP mice transplanted with wild-MNCs but not in wild-type mice transplanted with EGFP-MNCs.<BR>Discussion: This animal model resembles the typical clinical course of acute cerebral infarction followed by thrombolytic therapies in humans and could be used to examine new therapies after intra-arterial thrombolysis. In cerebral ischemia, just as in limb ischemia, transplanted MNCs did not differentiate into endothelial cells but instead promoted the formation of new vessels.<BR>Conclusion: In murine brain reperfused post ischemia, intra-arterial MNC transplantation promotes neovascularization. Furthermore, the new endothelial cells are derived from the recipient cells.

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