Comparative analysis on the anti-inflammatory/immune effect of mesenchymal stem cell therapy for the treatment of pulmonary arterial hypertension

Abstract

Despite the advancement of targeted therapy for pulmonary arterial hypertension (PAH), poor prognosis remains a reality. Mesenchymal stem cells (MSCs) are one of the most clinically feasible alternative treatment options. We compared the treatment effects of adipose tissue (AD)-, bone marrow (BD)-, and umbilical cord blood (UCB)-derived MSCs in the rat monocrotaline-induced pulmonary hypertension (PH) model. The greatest improvement in the right ventricular function was observed in the UCB-MSCs treated group. The UCB-MSCs treated group also exhibited the greatest improvement in terms of the largest decrease in the medial wall thickness, perivascular fibrosis, and vascular cell proliferation, as well as the lowest levels of recruitment of innate and adaptive immune cells and associated inflammatory cytokines. Gene expression profiling of lung tissue confirmed that the UCB-MSCs treated group had the most notably attenuated immune and inflammatory profiles. Network analysis further revealed that the UCB-MSCs group had the greatest therapeutic effect in terms of the normalization of all three classical PAH pathways. The intravenous injection of the UCB-MSCs, compared with those of other MSCs, showed superior therapeutic effects in the PH model for the (1) right ventricular function, (2) vascular remodeling, (3) immune/inflammatory profiles, and (4) classical PAH pathways.

MSC Transplantation Attenuates Inflammation, Prevents Endothelial Damage and Enhances the Angiogenic Potency of Endogenous MSCs in a Model of Pulmonary Arterial Hypertension

“… 8–11 Numerous preclinical studies demonstrated promising therapeutic potential of MSC therapy for PAH; however, the majority of the studies was conducted by using the monocrotaline (MCT) model. 12 Notably, this model does not recapitulate all the histopathological alterations observed in human PAH, such as neointimal and plexogenic arteriopathy. 13 , 14 Furthermore, many drugs that have demonstrated efficacy in the MCT models have failed to show clinical benefit in human trial.…”

Stem Cell and Exosome Therapy in Pulmonary Hypertension

“…Among them, MSCs separated from umbilical cord blood were found to have superior effects in terms of improving right ventricular function, pathological changes, cell engraftment, anti-inflammatory aspects. 32) These stem cells regulate the immune/inflammatory response in the MCT model, thereby improving the environment (niche) in which stem cells live and increasing the survival rate of stem cells. Stem cells with an increased survival rate persist for a long time to exert their function, alleviate the inflammatory response, attenuate vascular remodeling in the PH model, and improve hemodynamic function.…”

Application of adipose-derived stem cells in treating fibrosis

“…Mesenchymal stem cells from adipose tissue (ASCs), bone marrow (BMSCs) and umbilical cord blood (UCB-MSCs) were compared. As a result, UCB-MSCs proved to be the most effective in treating PAH, exhibiting the greatest improvement in cardiac function as well as reductions in fibrosis, inflammation, and classic PAH pathways[ 62 ]. It is interesting that MSCs from different sources vary so much in their effects.…”