Mesenchymal stromal cells for improvement of cardiac function following acute myocardial infarction: a matter of timing

Physiol Rev. 2023 Aug 17. doi: 10.1152/physrev.00009.2023. Online ahead of print.ABSTRACTAcute myocardial infarction (AMI) is the leading cause of cardiovascular death and remains the most common cause of heart failure (HF). Re-opening of the occluded artery i.e., reperfusion, is the only way to save the myocardium. However, the expected benefits on infarct size are disappointing due to the reperfusion paradox, which also induces specific cell death. These ischemia-reperfusion (IR) lesions can account for up to 50% of final infarct size, a major determinant for both mortality and the risk of heart failure (morbidity). In this review, we first provide a detailed description of the cell death and inflammation mechanisms as features of IR injury, cardioprotective strategies such as ischemic postconditioning (PostC) as well as their underlying mechanisms. Due to their biological properties, the use of Mesenchymal Stromal/Stem Cells (MSC) has been considered as a potential therapeutic approach in AMI. Despite promising results and evidence of safety in preclinical studies using MSC, the effects reported in clinical trials are not conclusive and even inconsistent. These discrepancies were attributed to many parameters such as donor age, in vitro culture and storage time as well as injection time window after AMI, which alter MSC therapeutic properties. In the context of AMI, future directions will be to generate MSC with enhanced properties in order to limit cell death in myocardia...
Source: Physiological Reviews - Category: Physiology Authors: Source Type: research