Comparison of angiogenic potency between mesenchymal stem cells and mononuclear cells in a rat model of hindlimb ischemia.
OBJECTIVE
Mesenchymal stem cells (MSC) are pluripotent cells that differentiate into a variety of cells including endothelial cells and vascular smooth muscle cells. Although transplantation of bone marrow-derived mononuclear cells (MNC) has already been applied for the treatment of critical limb ischemia, little information is available regarding comparison of the angiogenic potency between MSC and MNC. Accordingly, we injected equal numbers of MSC or MNC in a rat model of hindlimb ischemia and compared their therapeutic potential.


RESULTS
Immediately after creating hindlimb ischemia, rats were randomized to receive MSC transplantation (MSC group), MNC transplantation (MNC group), or vehicle infusion (Control group). Three weeks after transplantation, the laser Doppler perfusion index was significantly higher in the MNC group than in the Control group (0.69+/-0.1 vs. 0.57+/-0.06, P<0.01). Furthermore, there was a marked improvement in blood perfusion in the MSC group (0.81+/-0.08). Capillary density was highest in the MSC group. The number of transplanted cell-derived endothelial cells was higher in the MSC group than in the MNC group. Transplanted cell-derived vascular smooth muscle cells were detected only in the MSC group. In vitro, MSC were more tolerant to apoptotic stimulus (serum starvation and hypoxia) than MNC.


CONCLUSIONS
MSC transplantation caused significantly greater improvement in hindlimb ischemia than MNC transplantation. Compared with MNC, MSC survived well under an ischemic environment, and differentiated into not only endothelial cells but also vascular smooth muscle cells. Thus, MSC transplantation may be a new therapeutic strategy for the treatment of severe peripheral vascular disease.
Iwase
Takashi
T
Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, Suita, Osaka, Japan.
Nagaya
Noritoshi
N
Fujii
Takafumi
T
Itoh
Takefumi
T
Murakami
Shinsuke
S
Matsumoto
Toshio
T
Kangawa
Kenji
K
Kitamura
Soichiro
S
D000818:Animals; D017209:Apoptosis; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D042783:Endothelial Cells / Q000473:pathology; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D017078:Laser-Doppler Flowmetry; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D018919:Neovascularization, Physiologic; D016491:Peripheral Vascular Diseases / Q000628:therapy; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D014182:Transplantation, Autologous