Polymer Transfected Primary Myoblasts- Mediated Angiogenic Gene Therapy for Ischemic Heart Disease

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Publication Type dissertation
School or College College of Pharmacy
Department Pharmaceutics & Pharmaceutical Chemistry
Author Ou, Mei
Title Polymer Transfected Primary Myoblasts- Mediated Angiogenic Gene Therapy for Ischemic Heart Disease
Date 2010-02-10
Description Polymer transfected primary myoblasts-mediated angiogenic gene therapy is proposed as a new therapeutic regime for ischemic heart disease. The conventional drug therapy and surgical treatment can neither regenerate the lost myocardium nor restore the damaged blood supply after cardiac infarction. In the therapeutic regime to be developed, primary myoblasts, the progenitor cells existing in the skeletal muscle tissues, can differentiate and proliferate into contractile and functional myocardium when injected into the infracted heart muscle. They also provide effective cellular vehicles to express angiogenic genes of vascular endothelial growth factor (VEGF) to promote the formation of new blood vessels. As a result, the new functional myocardium and vasculature will be formed to restore the cardiac function which otherwise would be severely affected by scarring tissue formation. Poly(disulfide amine)s are designed and synthesized as a series of new biodegradable polymer nucleic acids carriers. They have defined structures: disulfide bonds in the main chain give these cationic polymers good biodegradability, which could then be rapidly degraded by disulfide-thiol exchange reaction with free thiol in the cytoplasm; amine groups in polymer structures give these novel polymers strong nucleic acid binding ability and buffering capacity. These features enable poly(disulfide amine)s of higher gene transfection efficiency and lower cytotoxicity than branched poly(ethylamine) (bPEI. 25kDa). Under in vitro conditions, one of poly(disulfide amine)s named poly(cystaminebisacryamide-diaminohexane) [poly(CBA-DAH)] has been evaluated as an optimal carrier to transfect angiogenic gene VEGF165 into primary myoblasts and stimulate endothelial proliferation. In the short-term animal studies, the myoblasts transfected with poly(CBA-DAH)/pCMV-VEGFi65 polyplexes are injected into the infracted zone on rat left ventricle, which is created through the left anterior descending (LAD) artery ligation. In 3 days post operation, ELISA assay detected higher VEGF,65 expression in transfected myoblasts injection group than in ligation only group. These studies verify polymer transfected primary myoblasts-mediated angiogenic gene therapy as a potential treatment strategy for ischemic heart disease.
Type Text
Publisher University of Utah
Subject Coronary Heart Disease; Myoblast Transfer Therapy
Subject MESH Gene Therapy; Coronary Disease; Myoblasts, Cardiac
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Polymer transfected primary myoblasts- mediated angiogenic gene therapy for ischemic heart disease." Spencer S. Eccles Health Sciences Library. Print version of "Polymer transfected primary myoblasts-mediated angiogenic gene therapy for ischemic heart disease." available at J. Willard Marriot Library Special Collection. RC39.5 2009.O88.
Rights Management © Mei Ou
Format Medium application/pdf
Format Extent 2,537,582 bytes
Source Original: University of Utah Spencer S. Eccles Health Sciences Library
Conversion Specifications Original scanned on Fujitsu fi-5220G as 400 dpi to pdf using ABBYY FineReader 10
ARK ark:/87278/s6z03psx
Setname ir_etd
Date Created 2012-04-23
Date Modified 2012-04-23
ID 193848
Reference URL https://collections.lib.utah.edu/ark:/87278/s6z03psx