San Diego State University, SDSU Heart Institute, Department of Biology, San Diego, CA 92182, USA.
Regen Med. 2009 Nov;4(6):823-33. doi: 10.2217/rme.09.51.
Cardiac stem cells (CSCs) show potential as a cellular therapeutic approach to blunt tissue damage and facilitate reparative and regenerative processes after myocardial infarction. Despite multiple published reports of improvement, functional benefits remain modest using normal stem cells delivered by adoptive transfer into damaged myocardium. The goal of this study is to enhance survival and proliferation of CSCs that have undergone lineage commitment in early phases as evidenced by expression of proteins driven by the alpha-myosin heavy chain (alphaMHC) promoter. The early increased expression of survival kinases augments expansion of the cardiogenic CSC pool and subsequent daughter progeny.
MATERIALS & METHODS: Normal CSCs engineered with fluorescent reporter protein constructs under control of the alphaMHC promoter show transgene protein expression, confirming activity of the promoter in CSCs. Cultured CSCs from both nontransgenic and cardiac-specific transgenic mice expressing survival kinases driven by the alphaMHC promoter were analyzed to characterize transgene expression following treatments to promote differentiation in culture.
RESULTS & CONCLUSION: Therapeutic genes controlled by the alphaMHC promoter can be engineered into and expressed in CSCs and cardiomyocyte progeny with the goal of improving the efficacy of cardiac stem cell therapy.
心脏干细胞（CSCs）作为一种细胞治疗方法，具有潜在的应用前景，可以减轻心肌梗死后的组织损伤，并促进修复和再生过程。尽管已经有多项关于改善功能的研究报道，但通过将正常的干细胞通过过继转移到受损的心肌中进行传递，其功能益处仍然有限。本研究的目的是增强心脏干细胞的存活和增殖，这些心脏干细胞在早期阶段已经经历了谱系分化，其证据是由α-肌球蛋白重链（αMHC）启动子驱动的蛋白表达。早期存活激酶的表达增加，会增加心肌生成性 CSC 池的扩张及其随后的子代产物。
用αMHC 启动子控制的荧光报告蛋白构建体工程化的正常 CSCs 显示转基因蛋白表达，证实启动子在 CSCs 中的活性。对来自非转基因和心脏特异性转基因小鼠的培养 CSCs 进行分析，这些小鼠的生存激酶由αMHC 启动子驱动，以在培养中促进分化的处理后分析转基因表达。
可以将受αMHC 启动子控制的治疗基因工程化并表达在 CSCs 和心肌细胞祖细胞中，以提高心脏干细胞治疗的效果。
