Therapeutic angiogenesis by transplantation of induced pluripotent stem cell-derived Flk-1 positive cells.
BACKGROUND
Induced pluripotent stem (iPS) cells are the novel stem cell population induced from somatic cells. It is anticipated that iPS will be used in the expanding field of regenerative medicine. Here, we investigated whether implantation of fetal liver kinase-1 positive (Flk-1+) cells derived from iPS cells could improve angiogenesis in a mouse hind limb model of ischemia.


RESULTS
Flk-1+ cells were induced from iPS cells after four to five days of culture. Hind limb ischemia was surgically induced and sorted Flk-1+ cells were directly injected into ischemic hind limbs of athymic nude mice. Revascularization of the ischemic hind limb was accelerated in mice that were transplanted with Flk-1+ cells compared with control mice, which were transplanted with vehicle, as evaluated by laser Doppler blood flowmetry. Transplantation of Flk-1+ cells also increased expression of VEGF mRNA in ischemic tissue compared to controls.


CONCLUSIONS
Direct local implantation of iPS cell-derived Flk-1+ cells would salvage tissues from ischemia. These data indicate that iPS cells could be valuable in the therapeutic induction of angiogenesis.
Suzuki
Hirohiko
H
Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8560, Japan.
Shibata
Rei
R
Kito
Tetsutaro
T
Ishii
Masakazu
M
Li
Ping
P
Yoshikai
Toru
T
Nishio
Naomi
N
Ito
Sachiko
S
Numaguchi
Yasushi
Y
Yamashita
Jun K
JK
Murohara
Toyoaki
T
Isobe
Kenichi
K
D000818:Animals; D002460:Cell Line; D002469:Cell Separation; D004195:Disease Models, Animal; D005121:Extremities / Q000098:blood supply* / Q000473:pathology / Q000601:surgery; D005434:Flow Cytometry; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D007511:Ischemia / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D018919:Neovascularization, Physiologic; D033581:Stem Cell Transplantation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis
D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2