From the Department of Pediatrics (R.J.V., J.D.M.).
From the Department of Pediatrics (R.J.V., J.D.M.)
Circ Res. 2018 Jul 6;123(2):159-176. doi: 10.1161/CIRCRESAHA.118.311208.
Death of adult cardiac myocytes and supportive tissues resulting from cardiovascular diseases such as myocardial infarction is the proximal driver of pathological ventricular remodeling that often culminates in heart failure. Unfortunately, no currently available therapeutic barring heart transplantation can directly replenish myocytes lost from the injured heart. For decades, the field has struggled to define the intrinsic capacity and cellular sources for endogenous myocyte turnover in pursuing more innovative therapeutic strategies aimed at regenerating the injured heart. Although controversy persists to this day as to the best therapeutic regenerative strategy to use, a growing consensus has been reached that the very limited capacity for new myocyte formation in the adult mammalian heart is because of proliferation of existing cardiac myocytes but not because of the activity of an endogenous progenitor cell source of some sort. Hence, future therapeutic approaches should take into consideration the fundamental biology of myocyte renewal in designing strategies to potentially replenish these cells in the injured heart.
由于心肌梗死等心血管疾病导致的成年心肌细胞和支持组织的死亡,是病理性心室重构的主要驱动因素,而病理性心室重构常常导致心力衰竭。不幸的是,目前除了心脏移植之外,尚无任何治疗方法可以直接补充因心脏损伤而丧失的心肌细胞。几十年来,该领域一直在努力定义内源性心肌细胞更新的固有能力和细胞来源,以寻求更具创新性的治疗策略,旨在使受损的心脏再生。尽管时至今日,对于使用哪种最佳的治疗性再生策略仍存在争议,但人们越来越达成共识,即成年哺乳动物心脏中新的心肌细胞形成的能力非常有限,这是因为现有心肌细胞的增殖,而不是某种内源性祖细胞来源的活性。因此,未来的治疗方法应该考虑心肌更新的基础生物学,在设计策略时,要考虑有可能在受损心脏中补充这些细胞。