Stem Cell Therapies and Treatment Advances for Heart Failure with Preserved Ejection Fraction

Abstract

Heart failure with preserved ejection fraction (HFpEF) is characterized by a left ventricular ejection fraction of 50% or greater. While heart failure with reduced ejection fraction (HFrEF) is well-characterized and has numerous treatment options, HFpEF remains poorly understood. HFpEF has long been termed diastolic dysfunction, because it was thought that fibrosis and impaired relaxation of the left ventricle could alone explain the underlying pathophysiology. However, recent research has identified additional mechanisms that influence HFpEF, specifically metabolic disorders and proinflammatory conditions. Despite this recent progress in elucidating the pathophysiology, there are still no approved treatment options that increase survival in patients with HFpEF. In the context of limited pharmacological options, stem cell therapy and cardiac biomarkers have emerged as potential breakthroughs in the treatment of HFpEF, but there has not yet been a review of their potential. This review evaluates the potential of cardiosphere-derived cells (CDCs), mesenchymal stromal cells (MSCs), and endothelial progenitor cells (EPCs) in the treatment of HFpEF. CDCs have shown promise, with a placebo-controlled animal trial demonstrating an increase in survival and a marked improvement in left ventricular end diastolic filling among the group treated with intracoronary infusion of CDCs. Additionally, with the newfound understanding of HFpEF pathophysiology, studies have also investigated the role MSCs and EPCs play in the inflammation associated with HFpEF, as well as the potential benefit these stem cells would bring to the treatment of HFpEF. While clinical trials are needed to confirm the safety and efficacy of these therapies, we offer insight into their potential, as well as a comprehensive summary of the pertinent clinical studies that are currently in progress. Embase, Ovid Medline, and PubMed were used to search all relevant literature for this review.

Extracellular vesicles secreted by human cardiosphere-derived cells attenuate electrophysiological remodelling in an in vitro model of atrial fibrillation

“…In this context of limited therapeutic efficacy and a high clinical need, the use of advanced therapies, including stem cell therapy, has emerged as a potential breakthrough [5].…”

“…This makes it necessary to keep developing new treatment strategies that target the underlying fundamental molecular pathways and try to trigger endogenous reparative responses. In this context of limited therapeutic efficacy of the available medicines for some specific cardiac conditions considered as unmet medical needs, the use of advanced therapy medicinal products (ATMPs), including stem cell therapy, extracellular vesicles (EVs) and biomaterials such as hydrogels has emerged as a potential breakthrough [5]. Contrary to current treatments, biological products could have the potential to treat cardiac aging-associated pathologies from a more fundamental level [110], as they are able to improve cell survival and protection, cell-cell communication, angiogenesis, cardiomyogenesis, reduce inflammation and molecularly regulate proliferation and cell cycle [79].…”

“…and biomaterials such as hydrogels emerged as a potential breakthrough for the treatment of cardiac pathologies [5] because contrary to current treatments, they have the potential to treat cardiac aging-associated pathologies from a more fundamental level [110]. They are able to improve cell survival and protection, cell-cell communication, angiogenesis, cardiomyogenesis, reduce inflammation and molecularly regulate proliferation and cell cycle [79].…”

“…However, current treatments present severe clinical efficacy and safety problems [2,3] and are not regarded as definitive cures [4]. The use of advanced therapies, including stem cell therapy, extracellular vesicles (EVs) and biomaterials such as hydrogels has emerged as a potential breakthrough [5]. Nevertheless, many problems and unknowns still remain that need to be solved before they can reach the clinical scenario.…”