The therapeutic impact of human neonatal BMSC in a right ventricular pressure overload model in mice

Abstract

Objective: To determine the impact of donor age on the therapeutic effect of bone marrow-derived mesenchymal stem cells (BMSCs) in treating adverse remodeling as the result of right ventricle (RV) pressure overload. Methods: BMSCs were isolated from neonatal (< 1 month), infant (1 month to 1 year), and young children (1 year to 5 years) and were compared in their migration potential, surface marker expression, VEGF secretion, and matrix metalloprotein (MMP) 9 expression. Four-week-old male C57 mice underwent pulmonary artery banding and randomized to treatment and untreated control groups. During the surgery, BMSCs were administered to the mice by intramyocardial injection into the RV free wall. Four weeks later, RV function and tissue were analyzed by echocardiography, histology, and quantitative real-time polymerase chain reaction.Results: Human neonatal BMSCs demonstrated the greatest migration capacity and secretion of vascular endothelial growth factor but no difference in expression of surface markers. Neonate BMSCs administration resulted in increasing expression of VEGF, a significant reduction in RV wall thickness, and internal diameter in mice after PA banding. These beneficial effects were probably associated with paracrine secretion as no cardiomyocyte transdifferentiation was observed.Conclusions: Human BMSCs from different age groups have different characteristics, and the youngest BMSCs may favorably impact the application of stem cell-based therapy to alleviate adverse RV remodeling induced by pressure overload.

Long-Term Sevoflurane Exposure Inhibits The Proliferation, Differentiation, and Homing Potential of Bone Marrow Mesenchymal Stem Cells

“…Sevoflurane is currently one of the most commonly used gas anesthetics for pediatric anesthesia [19,20]. However, because the proportion of BMSCs in children is significantly higher than that in adults [21,22], the effect of sevoflurane on the characteristics and functions of BMSCs may be a problem. To the best of knowledge, there are few convincing studies on the effect of sevoflurane on BMSCs.…”

Lithium and Copper Induce the Osteogenesis-Angiogenesis Coupling of Bone Marrow Mesenchymal Stem Cells via Crosstalk between Canonical Wnt and HIF-1α Signaling Pathways

“…And Wan et al have reported that HIF-1α could bind to the promoter region of osterix and promote osteoblast differentiation in MSCs [25]. So, we used the ChIP analysis which demonstrated that the osterix gene promoter 6 Stem Cells International region has obvious HIF-1α enrichment under the costimulation group and 25 μM Cu 2+ in the BMSCs (Figure 6(d), bar 3 versus bar 2, bar 1). Simultaneously, there was β-catenin enriched in VEGF's promoter region in the costimulation group and 500 μM Li + in the BMSCs (Figure 6(e)).…”

“…Currently, stem cell-based tissue engineering reconstruction of bone defect is a feasible and continuously developing strategy to restore structure and function [3]. Bone marrow mesenchymal stem cells (BMSCs), a seed of bone regeneration, can differentiate into osteoblasts and secrete angiogenic factors to promote bone regeneration [4][5][6]. Thus, the BMSCs have potential to couple the osteogenesis and angiogenesis processes.…”

The role of regenerative therapy in the treatment of right ventricular failure: a literature review

“…Most of our knowledge regarding the role of stem cells in the treatment of RV failure has been gleaned from studies in various experimental animal models of increased RV afterload, such as pulmonary artery banding (PAB), monocrotaline, or Sugen 5416/hypoxia models. To date, bone marrowderived mononuclear cells [30][31][32][33][34][35][36], umbilical cord blood-derived mononuclear cells [37][38][39][40], cardiospherederived cells, and cardiac progenitor cells [27,28,[41][42][43][44] have been tested in animal models as well as in human trials to address RV failure (Tables 1 and 2). Beneficial effects have been reported following administration of each of these cell types, but preclinical studies have lacked uniform experimental design (i.e., have varied route of administration, number of cells delivered, animal models or disease context, etc.…”

“…A few animal studies have been performed with bone marrow-derived mesenchymal stem cells (MSCs) targeting the RV with varying results. Attenuated RV hypertrophy and RV dimensions have been described following the administration of neonatal bone marrow-derived MSCs in a mouse PAB model [ 31 ]. In one report by Wehman et al, intramyocardial delivery of human bone marrow-derived MSCs in a neonatal pig RV pressure-overload PAB model resulted in enhanced angiogenesis, an increase in endogenous levels of c-kit+ putative cardiac stem cells, increased proliferation of cardiomyocytes and endothelial cells, reduced RV hypertrophy, and improved RV function compared to controls [ 32 ].…”