Approaches to repairing damaged myocardial tissue are complex and and multifactorial. One potential approach to restore cardiac function after myocardial infarction (MI) is through the use of cell-based therapies. However, the effectiveness of these therapies is still under debate. Recent studies, such as the one conducted by Qayyum et al. (1), have shown that the outcomes and effectiveness of cell-based therapies for heart disease are uncertain. In this particular study, 81 HFrEF patients received allogeneic adipose-derived mesenchymal stromal cells, and while the treatment was deemed safe in patients with ischemic heart disease, there was no significant improvement in LV function or clinical outcomes compared to the placebo.
Another clinical trial, the DREAM-HF trial (2), investigated the efficacy of cardiac cell therapy by randomizing 565 patients to either receive a sham procedure or stem cell therapy using allogenic mesenchymal precursor cells (MPCs). While the trial did not meet its primary and secondary endpoints, including time to recurrent decompensated heart failure-related events and all-cause death, it demonstrated that MPC therapy significantly reduced time-to-first event for MI or stroke over a mean follow-up of 30 months, especially in patients with evidence of systemic inflammation. Furthermore, stem cell therapy had a small but statistically significant beneficial effect on left ventricular ejection fraction in patients with elevated inflammation. The authors of the study suggest that MPC therapy primarily alters the inflammatory environment within the heart and vasculature by releasing anti-inflammatory factors and inducing microvascular network formation.
These studies highlight the need for further research to gain a better understanding of the mechanisms of action behind cell-based therapies and the importance of identifying biomarkers to improve patient selection.
The complex and dynamic interactions between implanted cells and the injured heart microenvironment have made it challenging to understand the mechanism of action of cell-based therapies for repairing damaged myocardial tissue. However, recent studies have shed light on the role of immune cells in the process of myocardial repair and regeneration after injury (3; 4). For example, Ding et al. (5) conducted a study that suggests transplanted human cord blood-derived unrestricted somatic stem cells (USSC) can modulate host immune-related events to improve healing after MI. The study found that T-cells play a crucial role in the immune response following MI, and the USSC-induced repair after ischemia/reperfusion was lost in rats without T-cells. Furthermore, the study found evidence of extensive formation of new myocytes, which may have resulted from the paracrine actions of the USSC secretome. These findings provide insights into the role of T cells that may be instrumental in triggering the regenerative response.
However, more research is necessary to identify specific T-cell subsets and paracrine signaling, as well as cells involved in the formation of cardiomyocytes, to optimize targeted cell therapy.
Another recent study, also included in this newsletter selection, by Zhang et al. (6) found that cardiac-resident macrophages (Mac1) can play a protective role in sepsis-induced cardiomyopathy by maintaining cardiac homeostasis through scavenging dysfunctional mitochondria ejected from cardiomyocytes. This process is associated with high levels of TREM2 expression. These findings underscore the importance of identifying specific immune cell populations and signaling pathways involved in cardiac repair and regeneration.
In summary, modulating immune cells such as T cells or macrophages holds promise as a therapeutic option for various cardiac diseases. However, further research is needed to better understand the mechanisms involved and optimize targeted cell therapy strategies. As these findings gain momentum, immune cell modulation may become an increasingly important approach to treating cardiac diseases.
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