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PubMed · 16159803

Maximizing ventricular function with multimodal cell-based gene therapy.

Terrence M Yau·Christopher Kim·Guangming Li·Yaoguang Zhang·Richard D Weisel·Ren-Ke Li
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Abstract

BACKGROUND: Angiogenesis is enhanced after transplantation of vascular endothelial growth factor (VEGF)-expressing cells into a myocardial scar. Insulin-like growth factor I (IGF-I) may induce hypertrophy and inhibit apoptosis. We evaluated the effect of cell-based IGF-I and VEGF multigene therapy on left ventricular (LV) function, cell survival, and apoptosis after bone marrow cell (BMC) transplantation. METHODS AND RESULTS: Female Lewis rats underwent left anterior descending ligation 3 weeks before transplantation with male donor BMC, BMC transfected with VEGF (BMC+VEGF), IGF-I (BMC+IGF-I), VEGF and IGF-I (BMC+VEGF+IGF-I), or medium without cells (control) (n=4 per group x 5 groups x 4 time points). Three days and 1, 2, and 4 weeks after transplantation, VEGF and IGF-I expression was quantitated by real-time polymerase chain reaction, cell survival by polymerase chain reaction for sry2, apoptosis by TUNEL staining, LV function by echocardiography and myosin heavy chain, and light chain and troponin I by Western blot. One week after transplantation, IGF-I expression in the scar and border zone was greatest in BMC+IGF-I and BMC+VEGF+IGF-I rats (P<0.05). VEGF expression in the scar and border zone was greatest in BMC+VEGF and BMC+VEGF+IGF-I hearts (P<0.05). Transplanted cell survival was lowest in BMC, intermediate in BMC+VEGF and BMC+IGF-I, and greatest in BMC+VEGF+IGF-I (P<0.05). Apoptotic indices were significantly reduced in BMC+VEGF+IGF-I, BMC+VEGF, and BMC+IGF-I (P<0.05). Two and 4 weeks after transplantation, LV ejection fraction was lowest in control, intermediate in BMC, BMC+VEGF, and BMC+IGF-I, and greatest in BMC+VEGF+IGF-I (P<0.05). CONCLUSIONS: Transplantation of VEGF- and IGF-I-expressing BMC reduced apoptosis, maximized transplanted cell survival, and enhanced LV function. Multimodal cell-based gene therapy may maximize the benefits of cell transplantation.

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AnimalsApoptosisBone Marrow CellsBone Marrow TransplantationCardiac MyosinsCell SurvivalCells, CulturedCicatrixFemaleGenetic TherapyGraft SurvivalInsulin-Like Growth Factor IMaleMesenchymal Stem Cell TransplantationMyocardial InfarctionMyocardiumMyosin Heavy ChainsMyosin Light ChainsNeovascularization, PhysiologicRatsRats, Inbred LewRecombinant Fusion ProteinsStroke VolumeTransfectionTroponin IUltrasonographyVascular Endothelial Growth Factor AVentricular Dysfunction, LeftVentricular Function, LeftComparative StudyEvaluation StudyJournal ArticleResearch Support, Non-U.S. Gov't

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Terrence M Yau, Christopher Kim, Guangming Li, Yaoguang Zhang, Richard D Weisel, Ren-Ke Li. 2005-08-30. Maximizing ventricular function with multimodal cell-based gene therapy.. https://doi.org/10.1161/circulationaha.104.525147

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