Emerging Strategies in Mesenchymal Stem Cell-Based Cardiovascular Therapeutics

Abstract

Cardiovascular diseases continue to challenge global health, demanding innovative therapeutic solutions. This review delves into the transformative role of mesenchymal stem cells (MSCs) in advancing cardiovascular therapeutics. Beginning with a historical perspective, we trace the development of stem cell research related to cardiovascular diseases, highlighting foundational therapeutic approaches and the evolution of cell-based treatments. Recognizing the inherent challenges of MSC-based cardiovascular therapeutics, which range from understanding the pro-reparative activity of MSCs to tailoring patient-specific treatments, we emphasize the need to refine the pro-regenerative capacity of these cells. Crucially, our focus then shifts to the strategies of the fourth generation of cell-based therapies: leveraging the secretomic prowess of MSCs, particularly the role of extracellular vesicles; integrating biocompatible scaffolds and artificial sheets to amplify MSCs' potential; adopting three-dimensional ex vivo propagation tailored to specific tissue niches; harnessing the promise of genetic modifications for targeted tissue repair; and institutionalizing good manufacturing practice protocols to ensure therapeutic safety and efficacy. We conclude with reflections on these advancements, envisaging a future landscape redefined by MSCs in cardiovascular regeneration. This review offers both a consolidation of our current understanding and a view toward imminent therapeutic horizons.

Keywords: cardiovascular therapeutics; cell-based therapy; extracellular vesicles; mesenchymal stem cells (MSCs); regenerative medicine.

Figure 1

Optimization strategies for enhanced MSC therapeutic efficacy in cardiovascular treatments. This diagram depicts the process of enhancing the efficacy of mesenchymal stem cells (MSCs) for cardiovascular applications. Unmodified MSCs face a hostile cellular environment, leading to reduced survival, premature senescence, and increased cell death, which collectively result in decreased therapeutic efficacy. On the other hand, MSCs undergoing preparation following GMP standards or genetically modified MSCs or MSCs preconditioned with growth factors, cytokines, or hypoxic conditions overcome the limitations of the unmodified state. The resultant modified MSCs exhibit enhanced adaptation to the injury environment, increased survival, and improved capacity for tissue regeneration, thus significantly improving therapeutic outcomes. The figure highlights the critical role of MSC optimization in advancing regenerative cardiovascular medicine. The figure above was partly generated using Servier Medical Art, provided by Servier, licensed under an unported Creative Commons Attribution 3.0 license.