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(Circulation. 2007;116:I-113 – I-120.)
© 2007 American Heart Association, Inc.

Myocardial Protection, Perioperative Management, and Vascular Biology

Transplantation of Nanoparticle Transfected Skeletal Myoblasts Overexpressing Vascular Endothelial Growth Factor-165 for Cardiac Repair

Lei Ye, MD, PhD; Husnain Kh Haider, PhD; RuSan Tan, MRCP; WeeChi Toh, Bsc; Peter K. Law, PhD; WeeBeng Tan, MSc; LiPing Su, Bsc; Wei Zhang, PhD; RuoWen Ge, PhD; Yong Zhang, PhD; YeanTeng Lim, MRCP; Eugene K.W. Sim, FRCS

From the National University Medical Institutes (L.Y., W.T.), National University of Singapore, Singapore; the Department of Pathology and Lab Medicine (H.K.H.), University of Cincinnati, Ohio; the National Heart Center (R.T., L.S., W.Z.), Singapore; Cell Transplants Singapore Pte. Ltd (P.K.L.), Singapore; the Department of Bioengineering (W.T., Y.Z.), National University of Singapore, Singapore; the Department of Biological Sciences (R.G.), National University of Singapore, Singapore; the Department of Cardiology (Y.L.), National University Hospital, Singapore; and the Department of Surgery (E.K.W.S.), National University of Singapore, Singapore & Gleneagles JPMC Cardiac Center, Brunei Darussalam.

Correspondence to A/Prof Eugene KW Sim, Department of Surgery, National University of Singapore, 10 Medical Drive, Singapore-117597. E-mail sursimkw{at}nus.edu.sg

Background— We investigated the feasibility and efficacy of polyethylenimine (PEI) based human vascular endothelial growth factor-165 (hVEGF₁₆₅) gene transfer into human skeletal myoblasts (HSM) for cell based delivery to the infarcted myocardium.

Methods and Results— Based on optimized transfection procedure using enhanced green fluorescent protein (pEGFP), HSM were transfected with plasmid-hVEGF₁₆₅ (phVEGF₁₆₅) carried by PEI (PEI- phVEGF₁₆₅) nanoparticles. The transfected HSM were characterized for transfection and expression of hVEGF₁₆₅ in vitro and transplanted into rat heart model of acute myocardial infarction (AMI): group-1=DMEM injection, group-2= HSM transplantation, group-3= PEI-phVEGF₁₆₅–transfected HSM (PEI-phVEGF₁₆₅ myoblast) transplantation. A total of 48 rats received cyclosporine injection from 3 days before and until 4 weeks after cell transplantation. Echocardiography was performed to assess the heart function. Animals were sacrificed for molecular and histological studies on the heart tissue at 4 weeks after treatment. Based on optimized transfection conditions, transfected HSM expressed hVEGF₁₆₅ for 18 days with >90% cell viability in vitro. Apoptotic index was reduced in group-2 and group-3 as compared with group-1. Blood vessel density (x400) by immunostaining for PECAM-1 in group-3 was significantly higher (P=0.043 for both) as compared with group-1 and group-2 at 4 weeks. Regional blood flow (ml/min/g) in the left ventricular anterior wall was higher in group-3 (P=0.043 for both) as compared with group-1 and group-2. Improved ejection fraction was achieved in group-3 (58.44±4.92%) as compared with group-1 (P=0.004).

Conclusion— PEI nanoparticle mediated hVEGF₁₆₅ gene transfer into HSM is feasible and safe. It may serve as a novel and efficient alternative for angiomyogenesis in cardiac repair.

Key Words: nanoparticle • polyethylenimine • VEGF₁₆₅ • skeletal myoblast • cardiac repair