Evidence for the therapeutic potential of ex vivo expanded human endothelial progenitor cells using autologous serum.
BACKGROUND
Transplantation of endothelial progenitor cell (EPC) augments angiogenesis in animal models of tissue ischemia. Although it is desirable to use expanded autologous EPCs for therapeutic angiogenesis in the clinical arena, a major obstacle is the limitation of the EPC expansion technique without using animal-derived serum such as fetal bovine serum (FBS). To overcome this issue, the possibility of human EPC (hEPCs) expansion using autologous serum (AS) culture was investigated.


RESULTS
Peripheral blood mononuclear cells were isolated from healthy volunteers by density-gradient centrifugation and culture-expanded in medium containing either FBS or AS. In vitro angiogenic functions, such as differentiation, migration and tube formation, were not significantly different between hEPCs cultured with FBS and AS. Next, we investigated whether transplantation of hEPCs would augment angiogenesis in unilateral hind limb ischemia using nude mice. The ratio of ischemic/normal limb blood flow and tissue capillary density in mice receiving hEPCs cultured with either FBS or AS significantly increased as compared with control mice receiving PBS alone. The ischemic/normal limb blood flow ratio and histological capillary density were not significantly different between hEPCs cultured with FBS and AS.


CONCLUSIONS
hEPCs can be culture-expanded in medium containing AS. Moreover, the angiogenic functions of such hEPCs are almost identical to those of hEPCs cultured with FBS. Ex vivo expanded hEPCs using AS seems to be useful for future clinical therapeutic angiogenesis.
Shumiya
Takanori
T
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Shibata
Rei
R
Shimizu
Yuuki
Y
Ishii
Masakazu
M
Kubota
Ryuji
R
Shintani
Satoshi
S
Murohara
Toyoaki
T
D000818:Animals; D002196:Capillaries / Q000473:pathology / Q000503:physiopathology; D002417:Cattle; D018929:Cell Culture Techniques; D004195:Disease Models, Animal; D042783:Endothelial Cells; D006614:Hindlimb / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018919:Neovascularization, Physiologic; D044967:Serum; D033581:Stem Cell Transplantation; D013234:Stem Cells; D014182:Transplantation, Autologous; D014183:Transplantation, Heterologous