Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Prog Mol Biol Transl Sci. 2012;111:195-215. doi: 10.1016/B978-0-12-398459-3.00009-5.
In animal models of myocardial infarction (MI), transplantation of various types of progenitor cells has been reported to (i) improve left ventricular (LV) function, (ii) decrease LV remodeling, (iii) limit fibrosis of noninfarcted LV regions, and (iv) in some cases, reduce infarct scar size. Moreover, in some reports these beneficial effects were present despite very low rates of long-term engraftment and transdifferentiation of transplanted cells into cardiomyocytes. In contrast, in other reports, significant numbers of transplanted cells do appear to have transdifferentiated into cardiomyocytes and vascular cells. Paracrine signals emanating from transplanted cells also appear to be very important because they protect injured cardiomyocytes and may activate endogenous cardiac progenitor cells (CPCs) to generate cardiomyocytes and vascular cells. Herein, we review evidence that transplanted bone-marrow- or cardiac-derived CPCs and/or in situ CPCs can be stimulated to propagate, differentiate, and partially replace cardiomyocytes damaged during AMI. The possibility that preexisting cardiomyocytes can be induced to reenter the cell cycle and regenerate replacement cardiomyocytes is also discussed.
在心肌梗死(MI)的动物模型中,已报道各种类型的祖细胞移植可:(i)改善左心室(LV)功能,(ii)减少 LV 重构,(iii)限制非梗死 LV 区域的纤维化,以及(iv)在某些情况下,减小梗死瘢痕的大小。此外,在一些报告中,尽管移植细胞的长期植入和向心肌细胞的转分化率非常低,但仍存在这些有益的效果。相比之下,在其他报告中,大量的移植细胞似乎确实已向心肌细胞和血管细胞转分化。源自移植细胞的旁分泌信号似乎也非常重要,因为它们可保护受损的心肌细胞,并可能激活内源性心脏祖细胞(CPCs)以生成心肌细胞和血管细胞。在此,我们回顾了证据,证明骨髓或心脏来源的 CPCs 和/或原位 CPCs 可被刺激增殖、分化,并部分替代 AMI 期间受损的心肌细胞。还讨论了诱导存在的心肌细胞重新进入细胞周期并再生替代心肌细胞的可能性。