Cardiomyocyte grafting for cardiac repair: Graft cell death and anti-death strategies
Cardiomyocyte grafting for cardiac repair: Graft cell death and anti-death strategies
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DOI：
10.1006/jmcc.2001.1367
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发表时间：
2001-05-01
影响因子：
5
通讯作者：
Murry, CE
中科院分区：
文献类型：
--
作者：
Zhang, M;Methot, D;Murry, CE
近年来的研究表明，心肌细胞移植可以在损伤的心脏中形成新的心肌。它是未知的。然而，是否可以产生生理上显著量的新心肌。初步实验表明，移植的新生大鼠心肌细胞的死亡限制了急性冷冻损伤后新心肌的形成。时间进程研究表明。在移植后30分钟，只有1.8（+/-0.4%）的移植细胞是TUNEL阳性的。第1天。然而，TUNEL指数增加至32.1（+/-3.5）%，并在4天时保持较高，平均为9.8（+/-3.8）%。到第7天，TUNEL下降至1.0（+/-0.2）%。电镜观察显示死亡细胞具有不可逆缺血损伤和凋亡的特征。为了测试缺血是否导致移植物存活率差，将移植物置于血管化的2周龄心脏肉芽组织或正常心肌中。TUNEL指数分别降低53%和86%。腺病毒感染的移植细胞与细胞保护激酶Akt。或组成型活性Akt。TUNEL指数分别降低31%和40%。与β-Gal转染的对照相比。与未处理对照相比，两种处理均未达到统计学显著性。然而，热休克减少心肌细胞死亡在体外的血清剥夺，葡萄糖消耗，和病毒激活的Pas死亡途径。当心肌细胞在移植前进行热休克处理时，在第1天，移植物细胞在体内的死亡减少了54%。因此，在移植到受损心脏后至少1天内发生高水平的心肌细胞死亡。很大程度上是由于缺血。死亡可以通过激活Akt通路来限制，甚至更有效地通过移植前的热休克来限制。(C)北京：科学出版社.
Recent studies indicate that cardiomyocyte grafting Forms new myocardium in injured hearts. It is unknown. However, whether physiologically significant amounts of new myocardium can be generated. Pilot experiments showed that death of grafted rat neonatal cardiomyocytes limited formation of new myocardium after acute cryoinjury. Time-course studies showed that. at 30 min after grafting, only 1.8(+/-0.4%) of graft cells were TUNEL-positive. At 1 day. however, TUNEL indices increased to 32.1(+/-3.5)% and remained high at 4 days, averaging 9.8(+/-3.8)%. By 7 days, TUNEL decreased to 1.0(+/-0.2)%. Electron microscopy revealed that dead cells had features of both irreversible ischemic injury and apoptosis. To test whether ischemia contributed to poor graft survival, grafts were placed into vascularized 2-week-old cardiac granulation tissue or normal myocardium. TUNEL indices were reduced by 53% and 86% respectively. Adenoviral infection of graft cells with the cytoprotective kinase Akt. or constitutively active Akt. reduced TUNEL indices by 31% and 40% respectively. compared to beta -gal-transfected controls. Neither treatment reached statistical significance compared to untreated controls. However, Heat shock reduced cardiomyocyte death in vitro in response to serum deprivation, glucose depletion, and viral activation of the Pas death pathway. When cardiomyocytes were heat shocked prior to grafting, graft cell death in vivo uas reduced by 54%, at day 1. Therefore, high levels of cardiomyocyte death occur for at least 1 days after grafting into injured hearts. in large part due to ischemia. Death can be limited by activating the Akt pathway and even more effectively by heat shock prior to transplantation. (C) 2001 Academic Press.