Stem cell therapy targeting the right ventricle in pulmonary arterial hypertension: is it a potential avenue of therapy?

Abstract

Pulmonary arterial hypertension (PAH) is an incurable disease characterized by an increase in pulmonary arterial pressure due to pathological changes to the pulmonary vascular bed. As a result, the right ventricle (RV) is subject to an increased afterload and undergoes multiple changes, including a decrease in capillary density. All of these dysfunctions lead to RV failure. A number of studies have shown that RV function is one of the main prognostic factors for PAH patients. Many stem cell therapies targeting the left ventricle are currently undergoing development. The promising results observed in animal models have led to clinical trials that have shown an improvement of cardiac function. In contrast to left heart disease, stem cell therapy applied to the RV has remained poorly studied, even though it too may provide a therapeutic benefit. In this review, we discuss stem cell therapy as a treatment for RV failure in PAH. We provide an overview of the results of preclinical and clinical studies for RV cell therapies. Although a large number of studies have targeted the pulmonary circulation rather than the RV directly, there are nonetheless encouraging results in the literature that indicate that cell therapies may have a direct beneficial effect on RV function. This cell therapy strategy may therefore hold great promise and warrants further studies in PAH patients.

Macrophage Immunomodulation: The Gatekeeper for Mesenchymal Stem Cell Derived-Exosomes in Pulmonary Arterial Hypertension?

“…Transplantation of different stem/progenitor cell types, for example, MSCs [ 54 , 55 , 56 , 57 ], induced pluripotent stem cells (iPS) [ 58 ], endothelial progenitor cells (EPCs) [ 59 , 60 , 61 ], and human amnion epithelial cells (AECs) [ 62 ], have effectively prevented, treated, and/or reversed core features of experimental PH and associated lung diseases where RVH occurs. Such cell-based therapies have been effective in providing protective, anti-inflammatory, regenerative, and improved functional outcomes (reviewed in [ 63 , 64 , 65 ]). Herein, we will focus on the application of MSC-based approaches in experimental PH.…”

Autologous skeletal myoblast patch implantation prevents the deterioration of myocardial ischemia and right heart dysfunction in a pressure-overloaded right heart porcine model

“…There have been multiple cell transplantation preclinical studies for RV dysfunction with various cell types, animal models, and administration methods [44,45]. However, so far, none of them have achieved clinical application.…”

Current and emerging therapeutic approaches to pulmonary hypertension

“…Indeed, recent preclinical studies suggested that regenerative cell-based therapies, gene therapies ( Fig. 4 ), and epigenetic medicines may offer a new perspective in the treatment of PAH ( Baliga et al, 2011 ; Brouwer et al, 2013 ; Ghofrani et al, 2009 ; Loisel et al, 2018 ).…”