Voges Holly K, Mills Richard J, Elliott David A, Parton Robert G, Porrello Enzo R, Hudson James E
School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland 4072, Australia.
Murdoch Children's Research Institute, Royal Children's Hospital, School of Biosciences, The University of Melbourne, Parkville, Victoria 3052, Australia.
Development. 2017 Mar 15;144(6):1118-1127. doi: 10.1242/dev.143966. Epub 2017 Feb 7.
The adult human heart possesses a limited regenerative potential following an ischemic event, and undergoes a number of pathological changes in response to injury. Although cardiac regeneration has been documented in zebrafish and neonatal mouse hearts, it is currently unknown whether the immature human heart is capable of undergoing complete regeneration. Combined progress in pluripotent stem cell differentiation and tissue engineering has facilitated the development of human cardiac organoids (hCOs), which resemble fetal heart tissue and can be used to address this important knowledge gap. This study aimed to characterize the regenerative capacity of immature human heart tissue in response to injury. Following cryoinjury with a dry ice probe, hCOs exhibited an endogenous regenerative response with full functional recovery 2 weeks after acute injury. Cardiac functional recovery occurred in the absence of pathological fibrosis or cardiomyocyte hypertrophy. Consistent with regenerative organisms and neonatal human hearts, there was a high basal level of cardiomyocyte proliferation, which may be responsible for the regenerative capacity of the hCOs. This study suggests that immature human heart tissue has an intrinsic capacity to regenerate.
成人心脏在缺血事件后具有有限的再生潜力，并会对损伤产生一系列病理变化。尽管斑马鱼和新生小鼠心脏中已记录到心脏再生，但目前尚不清楚未成熟的人类心脏是否能够完全再生。多能干细胞分化和组织工程的联合进展促进了人类心脏类器官（hCOs）的发展，其类似于胎儿心脏组织，可用于填补这一重要的知识空白。本研究旨在表征未成熟人类心脏组织对损伤的再生能力。在用干冰探针进行冷冻损伤后，hCOs在急性损伤后2周表现出内源性再生反应并实现完全功能恢复。心脏功能恢复发生在无病理性纤维化或心肌细胞肥大的情况下。与再生生物和新生人类心脏一致，心肌细胞增殖的基础水平较高，这可能是hCOs具有再生能力的原因。本研究表明，未成熟的人类心脏组织具有内在的再生能力。
