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Fetal Cardiac Cell Transplantation and Transcription Factor of the Heart

胎儿心肌细胞移植和心脏转录因子

基本信息

批准号：
07457299
负责人：
KITAMURA Soichiro
金额：
$ 3.71万
依托单位：
NARA MEDICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457299/
关键词：
GENE TRANSFER CELL TRANSPLANTATION RETROVIRUS ADENOVIRUS TRANSCRIPTION FACTOR FETAL CELLS CELL CYCLE 心筋細胞移植

项目摘要

Cardiac cell transplantation is the one potential treatment for acute or chronic heart failure with a significant loss of myocardium. Prerequisites for cellular transplantation to the heart to be successful include the followings : 1. formation of a new functional syncytium between grafted and host cardiomyocytes, 2. the number of grafted cells large enough to improve cardiac function, and 3. long-term graft survival. The transfer of a therapeutic gene into the cells to be grafted may possibly solve these obstacles. To begin with, we performed cell transplantation of the gene transferred fetal myocardial cells with recombinant plasmids, retroviruses, or adenoviruses coding beta-galactosidase. We found that adenovirus vector transduced the reporter gene into cultured cardiomyocytes without any damage, and that the grafted cardiac cells survived and expressed beta-gal for 12 weeks. The gap junctions were formed between the host cardiomyocytes and grafted cells. On the other hand, the plasmid vectors was little efficient for gene transfer, and the gene transferred grafted cells by the retroviruses could not form the gap junction in the host hearts. Candidates for gene transfer are the genes to make cardiomyocytes proliferate or to make embryonic cells differentiate into cardiomyocytes. However, the mechanisms of regulating the proliferation and differentiation of cardiomyocytes are unclear. We examined the expression patterns of cell cycle relating genes (Cyclin D1-3, Cyclin dependent kinase inhibitors (p15, p16, p21, p27, p57)) on P19 EC cells differentiating into cardiomyocytes under alpha MEM culture medium containing 1% DMSO.The results suggested that Cyclin D2 and p21 might play a role in induction of differentiation into cardiomyocytes. The function of p27 and p57 may be a strong inhibition of proliferation in process of differentiation into cardiomyocytes.

心肌细胞移植是治疗伴有心肌严重损失的急性或慢性心力衰竭的一种潜在治疗方法。心脏细胞移植成功的先决条件包括： 1. 移植心肌细胞和宿主心肌细胞之间形成新的功能性合胞体， 2. 移植细胞数量足够大以改善心脏功能，以及 3. 移植物长期存活。将治疗基因转移到要移植的细胞中可能会解决这些障碍。首先，我们用重组质粒、逆转录病毒或编码β-半乳糖苷酶的腺病毒对转入基因的胎儿心肌细胞进行细胞移植。我们发现腺病毒载体将报告基因转导到培养的心肌细胞中而没有任何损伤，并且移植的心肌细胞存活并表达β-gal达12周。宿主心肌细胞和移植细胞之间形成间隙连接。另一方面，质粒载体的基因转移效率较低，并且逆转录病毒转入基因的移植细胞不能在宿主心脏中形成间隙连接。基因转移的候选者是使心肌细胞增殖或使胚胎细胞分化为心肌细胞的基因。然而，调节心肌细胞增殖和分化的机制尚不清楚。我们检测了在含有 1% DMSO 的 α MEM 培养基中分化为心肌细胞的 P19 EC 细胞中细胞周期相关基因（Cyclin D1-3、Cyclin 依赖性激酶抑制剂（p15、p16、p21、p27、p57））的表达模式。结果表明，Cyclin D2 和 p21 可能在诱导分化为心肌细胞中发挥作用。心肌细胞。 p27和p57的功能可能是在心肌细胞分化过程中强烈抑制增殖。