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Sonic Hedgehog upregulation does not enhance the survival and engraftment of stem cell-derived cardiomyocytes in infarcted hearts.
PLOS ONE ( IF 3.7 ) Pub Date : 2020-01-16 , DOI: 10.1371/journal.pone.0227780
Jill J Weyers 1 , Jagadambika J Gunaje 1 , Benjamin Van Biber 1 , Amy Martinson 1 , Hans Reinecke 1 , William M Mahoney 1 , Stephen M Schwartz 1 , Timothy C Cox 2, 3 , Charles E Murry 1, 4, 5
Affiliation  

The engraftment of human stem cell-derived cardiomyocytes (hSC-CMs) is a promising treatment for remuscularizing the heart wall post-infarction, but it is plagued by low survival of transplanted cells. We hypothesize that this low survival rate is due to continued ischemia within the infarct, and that increasing the vascularization of the scar will ameliorate the ischemia and improve hSC-CM survival and engraftment. An adenovirus expressing the vascular growth factor Sonic Hedgehog (Shh) was injected into the infarcted myocardium of rats immediately after ischemia/reperfusion, four days prior to hSC-CM injection. By two weeks post-cell injection, Shh treatment had successfully increased capillary density outside the scar, but not within the scar. In addition, there was no change in vessel size or percent vascular volume when compared to cell injection alone. Micro-computed tomography revealed that Shh failed to increase the number and size of larger vessels. It also had no effect on graft size or heart function when compared to cell engraftment alone. Our data suggests that, when combined with the engraftment of hSC-CMs, expression of Shh within the infarct scar and surrounding myocardium is unable to increase vascularization of the infarct scar, and it does not improve survival or function of hSC-CM grafts.

中文翻译:

声波刺猬的上调不能增强梗死心脏中干细胞衍生的心肌细胞的存活和植入。

人干细胞源性心肌细胞(hSC-CMs)的植入是在梗死后使肌壁肌肉再生的一种有前途的治疗方法,但移植细胞存活率低困扰着它。我们假设这种低的存活率是由于梗塞内持续的缺血所致,并且增加疤痕的血管形成将改善缺血并改善hSC-CM的存活和植入。在hSC-CM注射前四天,在缺血/再灌注后立即将表达血管生长因子Sonic Hedgehog(Shh)的腺病毒注射到大鼠的梗塞心肌中。细胞注射后两周,Shh治疗已成功地增加了疤痕外而不是疤痕内的毛细血管密度。此外,与单独注射细胞相比,血管大小或血管体积百分比没有变化。微型计算机断层扫描显示Shh无法增加较大血管的数量和大小。与单独的细胞移植相比,它对移植物的大小或心脏功能也没有影响。我们的数据表明,当与hSC-CMs植入结合时,Shh在梗塞疤痕和周围心肌中的表达不能增加梗塞疤痕的血管形成,并且不能改善hSC-CM移植物的存活或功能。
更新日期:2020-01-17
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