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Ann Thorac Surg 2007;83:1119-1120
© 2007 The Society of Thoracic Surgeons
Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis St, Lowry Medical Office Building, Suite 2A Boston, MA 02215
(Email: jfeng{at}caregroup.harvard.edu; fsellke{at}caregroup.harvard.edu).
Yau and colleagues [1] report that the combination of bone marrow cell (BMC) transplantation with vascular endothelial growth factor/basic fibroblast growth factor (VEGF/bFGF) transgenes yields a synergistic effect on angiogeneisis in a rodent model of myocardial infarction. The authors found that mRNA of VEGF/bFGF was transiently expressed in BMC transfected with VEGF/bFGF transgenes, which leads to enhanced vascular density and improved regional perfusion and left ventricular contractile function. These novel findings suggest that multimodal cell-based gene therapy may be more useful in myocardial repair than unmodified cell-based therapy.
This is a well-designed and executed experimental study from a group that has previously published a number of elegant works in this exciting field of cell-based and gene-based cardiac repair. The results of the present study appear quite promising; however these results must be interpreted with caution because of the very small sample size. The authors performed a careful statistical analysis of these relatively small study groups. At 4 weeks, 6 rats were used and this number was sufficient to confirm their major findings. This is one of the first studies to investigate potentially synergistic effects of the combination of therapeutic VEGF/bFGF gene delivery with cell transplantation on angiogensis in an experimental model of the infarcted rat heart.
There is a growing body of evidence supporting the hypothesis that the release of paracrine growth factors and other potentially unknown cytokines from stem cells can promote neoangiogenesis [2]. The VEGF and bFGF are well-known angiogenic growth factors, and certainly the combination of the two may help to maximize the proliferation and differentiation of transplanted BMC and endogenous stem cells [3]. The combination of the two growth factors may synergistically protect the ischemic myocardium through similar or different molecular pathways. Although cell survival and VEGF/bFGF-protein expression were not evaluated, based on their previous findings, one speculates that the combination of the two factors may have an additive effect on improving cell survival and VEGF/bFGF-protein expression.
If gene or cell therapy is still in its infancy, multi-model cell-based gene therapy is just a newborn. Future studies should focus, in addition to other things, on developing less immunogenic and toxic vectors; controlling the level of transgene expression within transfected cells; optimizing the differentiation and proliferation of the stem cells; and regulating stem cell delivery, survival, and tissue integration. Another challenge will be to choose the appropriate applications that will allow a single stage, simple, and effective therapeutic approach with minimal potential for side effects [4, 5]. Thus more experimental and pre-clinical work is required before any significant clinical application can be expected.
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