von Bibra Constantin, Hinkel Rabea
Institute for Animal Hygiene, Animal Welfare and Farm Animal Behavior, Stiftung Tieraerztliche Hochschule Hannover, University of Veterinary Medicine, Hanover, Germany.
Laboratory Animal Science Unit, German Primate Center, Leibniz Institute for Primate Research, Goettingen, Germany.
Front Pharmacol. 2024 Jun 17;15:1408679. doi: 10.3389/fphar.2024.1408679. eCollection 2024.
Non-human primates (NHP) are valuable models for late translational pre-clinical studies, often seen as a last step before clinical application. The unique similarity between NHPs and humans is often the subject of ethical concerns. However, it is precisely this analogy in anatomy, physiology, and the immune system that narrows the translational gap to other animal models in the cardiovascular field. Cell and gene therapy approaches are two dominant strategies investigated in the research field of cardiac regeneration. Focusing on the cell therapy approach, several xeno- and allogeneic cell transplantation studies with a translational motivation have been realized in macaque species. This is based on the pressing need for novel therapeutic options for heart failure patients. Stem cell-based remuscularization of the injured heart can be achieved via direct injection of cardiomyocytes (CMs) or patch application. Both CM delivery approaches are in the late preclinical stage, and the first clinical trials have started. However, are we already ready for the clinical area? The present review concentrates on CM transplantation studies conducted in NHPs, discusses the main sources and discoveries, and provides a perspective about human translation.
非人灵长类动物(NHP)是后期转化临床前研究的宝贵模型,常被视为临床应用前的最后一步。NHP与人类之间独特的相似性常常引发伦理关注。然而,正是这种在解剖学、生理学和免疫系统方面的相似性,缩小了心血管领域与其他动物模型之间的转化差距。细胞和基因治疗方法是心脏再生研究领域中研究的两种主要策略。聚焦于细胞治疗方法,已经在猕猴物种中开展了多项具有转化意义的异种和同种异体细胞移植研究。这是基于对心力衰竭患者新型治疗选择的迫切需求。通过直接注射心肌细胞(CM)或贴片应用,可以实现基于干细胞的损伤心脏再肌化。这两种CM递送方法都处于临床前后期阶段,并且已经开始了首批临床试验。然而,我们是否已经为临床领域做好准备了呢?本综述集中讨论了在NHP中进行的CM移植研究,探讨了主要来源和发现,并提供了关于向人类转化的观点。