Transplantation of genetically engineered mesenchymal stem cells improves cardiac function in rats with myocardial infarction: benefit of a novel nonviral vector, cationized dextran.
It is expected that mesenchymal stem cells (MSCs) will be a cell source for cardiac reconstruction because of their differentiation potential and ability to supply growth factors. However, poor viability at the transplanted site often hinders the therapeutic potential of MSCs. Here, in a trial designed to address this problem, a non-viral carrier of cationized polysaccharide is introduced for genetic engineering of MSCs. Spermine-introduced dextran of cationized polysaccharide (spermine-dextran) was internalized into MSCs by way of a sugar-recognizable receptor to enhance the expression level of plasmid deoxyribonucleic acid (DNA). When genetically engineered by the spermine-dextran complex with plasmid DNA of adrenomedullin (AM), MSCs secreted a large amount of AM, an anti-apoptotic and angiogenic peptide. Transplantation of AM gene-engineered MSCs improved cardiac function after myocardial infarction significantly more than MSCs alone. Thus, this genetic engineering technology using the non-viral spermine-dextran is a promising strategy to improve MSC therapy for ischemic heart disease.
Jo
Jun-Ichiro
J
Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
Nagaya
Noritoshi
N
Miyahara
Yoshinori
Y
Kataoka
Masaharu
M
Harada-Shiba
Mariko
M
Kangawa
Kenji
K
Tabata
Yasuhiko
Y
D053607:Adrenomedullin / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002412:Cations; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D003911:Dextrans / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D024861:Genetic Enhancement / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D009203:Myocardial Infarction / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology / Q000601:surgery*; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function; D014162:Transfection / Q000379:methods*; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology / Q000601:surgery; D014780:Viruses / Q000235:genetics
D002412:Cations; D003911:Dextrans; D004337:Drug Carriers; D053607:Adrenomedullin; D004247:DNA