[Gelatin microspheres containing vascular endothelial growth factor enhances the efficacy of bone marrow mesenchymal stem cells transplantation in a swine model of myocardial infarction.].
OBJECTIVE
To investigate the efficacy of transplantation of mesenchymal stem cells (MSC) with gelatin microspheres containing vascular endothelial growth factor in ischemic regions in infracted swine hearts.


METHODS
Twelve Chinese mini swines with infarction were randomized to receive autogenetic MSC injection to the peri-infarction area of left ventricular wall (MSC group, n = 6) or MSC transplantation with gelatin hydrogel microspheres incorporating vascular endothelial growth factor (VEGF-MSC group, n = 6). Three weeks later, left ventricular function was assessed by magnetic resonance imaging (MRI). The contrast of the MSC hypointense lesion was determined using the difference in signal intensity between the hypointense and normal myocardium divided by signal intensity of the normal region. Myocardial capillary density, the number of DAPI positive MSC and the apoptotic MSC were also determined.


RESULTS
The diameter of the microspheres averaged (104.0 +/- 22.6) microm. At 24 hours after transplantation, MSC were identified by MRI as large intramyocardial signal voids at injection sites which persisted up to 3 weeks. There was no significant difference in the contrast of the lesions and in the size of the lesions at 24 hours between two groups. At 3 weeks after injection, the size of the lesions and the contrast of the lesion were decreased (P < 0.05) in both groups. The capillary density of the injection site was significantly more in the MSC-VEGF microsphere group than that in MSC group [(15.2 +/- 5.4)/HPF vs. (10.2 +/- 5.0)/HPF, t = 2.43, P < 0.05], and there were more dense DAPI labeled MSC per high power fields in injection sites of MSC-VEGF microsphere group than that in MSC group [(354 +/- 83)/HPF vs. (278 +/- 97)/HPF, t = 3.14, P < 0.05]. Moreover, the apoptosis rate of MSCs of MSCs-VEGF microsphere group was less than that of MSC group [(6.4 +/- 4.1)% vs. (11.9 +/- 4.8)%, t = 2.97, P < 0.05].


CONCLUSIONS
MSC transplantation with gelatin hydrogel microspheres incorporating VEGF enhanced the efficacy of MSC in this swine model of myocardial infarction. MRI tracking of MSC is feasible and represents a preferred method for studying the engraftment of MSCs in infracted tissue.
Department of Radiology, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
Qiong
Q
Liu
Shi-Hua
SH
Zhao
Min-Jie
MJ
Lu
Shi-Liang
SL
Jiang
Chao-Wu
CW
Yan
Yan
Y
Zhang
Liang
L
Meng
Yue
Y
Tang
Xian-Min
XM
Meng
Ying-Jie
YJ
Wei
Lin-Lin
LL
Wang
Hong-Jun
HJ
Dai
Jian
J
Xu
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D005780:Gelatin; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D008863:Microspheres; D009203:Myocardial Infarction; D013552:Swine; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A; D005780:Gelatin