title: Augmented neovascularization with magnetized endothelial progenitor cells in rats with hind-limb ischemia.
abstract: Augmenting neovascularization with the use of endothelial progenitor cells (EPCs) is a therapeutic option to rescue critical limb ischemia (CLI). However, the outcomes have been not so satisfactory. The detectable number of injected EPCs at the ischemic site is rather small. If EPCs accumulate more and stay longer there, neovascularization will be augmented. In this study, we tested whether external magnetic forces (EMFs) accumulated magnetized EPCs (Mag-EPCs) at the ischemic site and thereby augmented neovascularization. We cultured peripheral blood-derived mononuclear cells to obtain EPCs and generated Mag-EPCs by a magnetofection method with nanoparticles. Prussian-blue staining revealed magnetic nanoparticles incorporated into the cytoplasms and nuclei of Mag-EPCs. The survival rate of Mag-EPCs at day 9 of culture was 98.7%, indicating no cell toxicity of magnetic nanoparticles. EMFs augmented adhesion capacity of Mag-EPCs not only in the static but also in the flow condition in vitro, compared to without EMFs. The migration capacity of Mag-EPCs with EMFs was 160% more than EPCs or Mag-EPCs without them. After an intravenous injection of Mag-EPCs into the rat with hind-limb ischemia, the recovery of blood flow and capillary density in the ischemic limb were significantly more (p<0.01) with EMFs than without them. EMFs augmented neovascularization capacity of Mag-EPCs compared to EPCs alone. This method could be a new therapeutic strategy for patients with CLI.
authors: Division of Cardio-Vascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi 67, Kurume 830-0011, Japan.
authors: Hiroshi
authors: H
authors: Koiwaya
authors: Ken-ichiro
authors: K
authors: Sasaki
authors: Takafumi
authors: T
authors: Ueno
authors: Shinji
authors: S
authors: Yokoyama
authors: Yasuyuki
authors: Y
authors: Toyama
authors: Masanori
authors: M
authors: Ohtsuka
authors: Takaharu
authors: T
authors: Nakayoshi
authors: Yoshiaki
authors: Y
authors: Mitsutake
authors: Tsutomu
authors: T
authors: Imaizumi
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology; D006614:Hindlimb / Q000098:blood supply*; D006801:Humans; D007511:Ischemia / Q000628:therapy*; D008280:Magnetics; D058185:Magnetite Nanoparticles; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051381:Rats; D011923:Rats, Nude; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
chemical_list: D016207:Cytokines; D058185:Magnetite Nanoparticles