Cardiology Department, Santa Cruz Hospital, West Lisbon Hospital Center, Lisbon, Portugal; Hospital da Luz Lisboa, Luz Saúde, Lisbon, Portugal; Nova Medical School, Lisbon, Portugal.
Department of Cardiac Surgery, University Hospital Centre São João, Porto, Portugal; Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal.
Cytotherapy. 2021 Nov;23(11):974-979. doi: 10.1016/j.jcyt.2021.05.002. Epub 2021 Jun 7.
Although biologically appealing, the concept of tissue regeneration underlying first- and second-generation cell therapies has failed to translate into consistent results in clinical trials. Several types of cells from different origins have been tested in pre-clinical models and in patients with acute myocardial infarction (AMI). Mesenchymal stromal cells (MSCs) have gained attention because of their potential for immune modulation and ability to promote endogenous tissue repair, mainly through their secretome. MSCs can be easily obtained from several human tissues, the umbilical cord being the most abundant source, and further expanded in culture, making them attractive as an allogeneic "of-the-shelf" cell product, suitable for the AMI setting. The available evidence concerning umbilical cord-derived MSCs in AMI is reviewed, focusing on large animal pre-clinical studies and early human trials. Molecular and cellular mechanisms as well as current limitations and possible translational solutions are also discussed.
虽然从生物学角度来看很有吸引力,但第一代和第二代细胞疗法所基于的组织再生概念未能在临床试验中转化为一致的结果。已经在临床前模型和急性心肌梗死 (AMI) 患者中测试了几种来自不同来源的细胞。间充质基质细胞 (MSCs) 因其潜在的免疫调节能力和促进内源性组织修复的能力而受到关注,主要通过其分泌组实现。MSCs 可以从几种人体组织中轻松获得,其中脐带是最丰富的来源,并且可以在培养中进一步扩增,因此它们作为同种异体的“现成”细胞产品很有吸引力,适合 AMI 环境。本文综述了脐带来源的 MSCs 在 AMI 中的应用,重点介绍了大型动物临床前研究和早期人体试验。还讨论了分子和细胞机制以及当前的局限性和可能的转化解决方案。