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.

中文翻译：

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人类新生儿BMSC在小鼠右心室压力超负荷模型中的治疗作用。

目的确定供体年龄对骨髓间充质干细胞（BMSCs）治疗右心室（RV）压力超负荷所致不良重塑的治疗效果的影响。方法从新生儿（<1个月），婴儿（1个月至1岁）和幼儿（1岁至5岁）中分离BMSC，并比较它们的迁移潜能，表面标志物表达，VEGF分泌和基质金属蛋白（ MMP）9表达。四周大的雄性C57小鼠进行了肺动脉束带术，并随机分为治疗组和未治疗对照组。在手术期间，通过心肌内注射到无RV壁中向小鼠施用BMSC。四周后，通过超声心动图，组织学和实时定量聚合酶链反应分析RV功能和组织。结果人类新生儿骨髓间充质干细胞显示出最大的迁移能力和血管内皮生长因子的分泌，但表面标志物的表达没有差异。PA绑扎后，新生BMSCs的施用导致VEGF的表达增加，RV壁厚的显着减少以及小鼠的内径。这些有益的作用可能与旁分泌有关，因为未观察到心肌细胞转分化。结论不同年龄组的人骨髓间充质干细胞具有不同的特征，最年轻的骨髓间充质干细胞可能有利于影响干细胞疗法减轻压力超负荷引起的右室重构的应用。