Stem cell therapy with overexpressed VEGF and PDGF genes improves cardiac function in a rat infarct model.
BACKGROUND
Therapeutic potential was evaluated in a rat model of myocardial infarction using nanofiber-expanded human cord blood derived hematopoietic stem cells (CD133+/CD34+) genetically modified with VEGF plus PDGF genes (VIP).


RESULTS
Myocardial function was monitored every two weeks up to six weeks after therapy. Echocardiography revealed time dependent improvement of left ventricular function evaluated by M-mode, fractional shortening, anterior wall tissue velocity, wall motion score index, strain and strain rate in animals treated with VEGF plus PDGF overexpressed stem cells (VIP) compared to nanofiber expanded cells (Exp), freshly isolated cells (FCB) or media control (Media). Improvement observed was as follows: VIP>Exp> FCB>media. Similar trend was noticed in the exercise capacity of rats on a treadmill. These findings correlated with significantly increased neovascularization in ischemic tissue and markedly reduced infarct area in animals in the VIP group. Stem cells in addition to their usual homing sites such as lung, spleen, bone marrow and liver, also migrated to sites of myocardial ischemia. The improvement of cardiac function correlated with expression of heart tissue connexin 43, a gap junctional protein, and heart tissue angiogenesis related protein molecules like VEGF, pNOS3, NOS2 and GSK3. There was no evidence of upregulation in the molecules of oncogenic potential in genetically modified or other stem cell therapy groups.


CONCLUSIONS
Regenerative therapy using nanofiber-expanded hematopoietic stem cells with overexpression of VEGF and PDGF has a favorable impact on the improvement of rat myocardial function accompanied by upregulation of tissue connexin 43 and pro-angiogenic molecules after infarction.
Das
Hiranmoy
H
The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA. hiranmoy.das@osumc.edu
George
Jon C
JC
Joseph
Matthew
M
Das
Manjusri
M
Abdulhameed
Nasreen
N
Blitz
Anna
A
Khan
Mahmood
M
Sakthivel
Ramasamy
R
Mao
Hai-Quan
HQ
Hoit
Brian D
BD
Kuppusamy
Periannan
P
Pompili
Vincent J
VJ
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D018952:Antigens, CD34 / Q000096:biosynthesis; D018031:Connexin 43 / Q000096:biosynthesis; D004195:Disease Models, Animal; D004452:Echocardiography / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D006023:Glycoproteins / Q000096:biosynthesis; D008297:Male; D009203:Myocardial Infarction / Q000628:therapy*; D009389:Neovascularization, Pathologic; D010455:Peptides; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats; D011923:Rats, Nude; D033581:Stem Cell Transplantation / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics*
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D018031:Connexin 43; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D010982:Platelet-Derived Growth Factor; C000606025:Prom1 protein, rat; D042461:Vascular Endothelial Growth Factor A