Sex of Muscle Stem Cells Does Not Influence Potency for Cardiac Cell Therapy
Sex of Muscle Stem Cells Does Not Influence Potency for Cardiac Cell Therapy
复制标题
DOI：
10.3727/096368909x471305
复制
发表时间：
2009-01-01
影响因子：
3.3
通讯作者：
Huard, Johnny
中科院分区：
文献类型：
--
作者：
Drowley, Lauren;Okada, Masaho;Huard, Johnny
我们之前已经证明，骨骼肌源性干细胞(MDSCs)群体在骨骼肌和骨修复方面表现出基于性别的差异，女性细胞在骨骼肌中表现出比男性更强的移植能力，而男性细胞向成骨和软骨来源的分化更强劲。在这项研究中，我们验证了一种假设，即MDSCs移植到心肌中的治疗能力受到供者或受者性别的影响。将从3周龄小鼠骨骼肌分离的雄性和雌性MDSCs分别移植到受体雄性或雌性dystrophin缺陷型(MDX)心脏或急性心肌梗死后雄性SCID小鼠的心脏中。在MDX模型中，基于供体细胞或受体性别的植入或血管形成没有差异。在梗死模型中，与载体对照组相比，移植MDSC的心脏显示出更多的梗死后血管生成，更少的心肌疤痕形成，以及改善的心功能。然而，供体MDSCs的性别对植入、血管生成和心功能没有显著影响。血管内皮生长因子是一种强有力的血管生成因子，在男性和女性MDSCs中的表达相似。我们的结果表明，供者的MDSC或受体的性别对MDSC触发的心脏损伤后的心肌植入或再生的效率没有显著影响。MDSCs在不分化为心脏谱系的情况下通过促进血管生成来改善心脏再生和修复的能力可能是这些模型中观察到的性别差异缺乏的原因之一。
We have previously shown that populations of skeletal muscle-derived stem cells (MDSCs) exhibit sex-based differences for skeletal muscle and bone repair, with female cells demonstrating superior engrafting abilities to males in skeletal muscle while male cells differentiating more robustly toward the osteogenic and chondrogenic lineages. In this study, we tested the hypothesis that the therapeutic capacity of MDSCs transplanted into myocardium is influenced by sex of donor MDSCs or recipient. Male and female MDSCs isolated from the skeletal muscle of 3-week-old mice were transplanted into recipient male or female dystrophin-deficient (mdx) hearts or into the hearts of male SCID mice following acute myocardial infarction. In the mdx model, no difference was seen in engraftment or blood vessel formation based on donor cell or recipient sex. In the infarction model, MDSC-transplanted hearts showed higher postinfarction angiogenesis, less myocardial scar formation, and improved cardiac function compared to vehicle controls. However, sex of donor MDSCs had no significant effects on engraftment, angiogenesis, and cardiac function. VEGF expression, a potent angiogenic factor, was similar between male and female MDSCs. Our results suggest that donor MDSC or recipient sex has no significant effect on the efficiency of MDSC-triggered myocardial engraftment or regeneration following cardiac injury. The ability of the MDSCs to improve cardiac regeneration and repair through promotion of angiogenesis without differentiation into the cardiac lineage may have contributed to the lack of sex difference observed in these models.