Cardiac stem cell genetic engineering using the alphaMHC promoter.
Cardiac stem cell genetic engineering using the alphaMHC promoter.
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DOI：
10.2217/rme.09.51
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发表时间：
2009-11
影响因子：
2.7
通讯作者：
Sussman MA
中科院分区：
文献类型：
--
作者：
Bailey B;Izarra A;Alvarez R;Fischer KM;Cottage CT;Quijada P;Díez-Juan A;Sussman MA
心脏干细胞（CSCs）显示出作为细胞治疗方法的潜力，以钝化组织损伤，并促进心肌梗死后的修复和再生过程。尽管有多个已发表的改善报告，但使用通过过继转移递送到受损心肌中的正常干细胞的功能益处仍然有限。本研究的目的是提高在早期阶段经历谱系定型的CSC的存活和增殖，这通过α-肌球蛋白重链（αMHC）启动子驱动的蛋白质的表达来证明。存活激酶的早期表达增加增加了心源性CSC库和随后的子代的扩增。用αMHC启动子控制下的荧光报告蛋白构建体工程化的正常CSC显示转基因蛋白表达，证实了启动子在CSC中的活性。对来自表达由αMHC启动子驱动的存活激酶的非转基因小鼠和心脏特异性转基因小鼠的培养CSC进行分析，以表征处理以促进培养物分化后的转基因表达。由αMHC启动子控制的治疗基因可以被工程化到CSC和心肌细胞后代中并在其中表达，目的是提高心脏干细胞治疗的功效。
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 α-myosin heavy chain (αMHC) promoter. The early increased expression of survival kinases augments expansion of the cardiogenic CSC pool and subsequent daughter progeny. Normal CSCs engineered with fluorescent reporter protein constructs under control of the αMHC 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 αMHC promoter were analyzed to characterize transgene expression following treatments to promote differentiation in culture. Therapeutic genes controlled by the αMHC promoter can be engineered into and expressed in CSCs and cardiomyocyte progeny with the goal of improving the efficacy of cardiac stem cell therapy.
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影响因子：
24
作者：
Li, Zongjin;Lee, Andrew;Huang, Mei;Chun, Hyung;Chung, Jaehoon;Chu, Pauline;Hoyt, Grant;Yang, Phillip;Rosenberg, Jarrett;Robbins, Robert C.;Wu, Joseph C.
通讯作者：
Wu, Joseph C.
DOI：
10.1073/pnas.0706406104
发表时间：
2007-11-06
影响因子：
11.1
作者：
Rota, Marcello;Kajstura, Jan;Anversa, Piero
通讯作者：
Anversa, Piero
影响因子：
20.1
作者：
Haider, Husnain Kh;Jiang, Shujia;Ashraf, Muhammad
通讯作者：
Ashraf, Muhammad
DOI：
10.1073/pnas.0510138103
发表时间：
2006-08-08
影响因子：
11.1
作者：
Tsujita, Yasuyuki;Muraski, John;Sussman, Mark A.
通讯作者：
Sussman, Mark A.
影响因子：
20.1
作者：
Gude, Natalie;Muraski, John;Sussman, Mark A.
通讯作者：
Sussman, Mark A.