Department of Pathophysiology, Tongji Medical College, Huazhong Science and Technology University, Wuhan, People's Republic of China.
Cardiovasc Res. 2013 Oct 1;100(1):19-27. doi: 10.1093/cvr/cvt165. Epub 2013 Jun 25.
Pulmonary arterial hypertension, a chronic lung disease, remains an unacceptable prognosis despite significant advances in conventional therapies. Stem cell therapy represents a novel and effective modality. This study was aimed to add new insight in gender differences of bone marrow-derived mesenchymal stem cells on therapy against pulmonary arterial hypertension and the underlying mechanism.
By in vivo experiments, we showed for the first time female bone marrow-derived mesenchymal stem cells possessed a better therapeutic potential against monocrotaline-induced pulmonary arterial hypertension in C57BL/6J mice compared with male counterparts. In vitro experiments demonstrated superior function of female bone marrow-derived mesenchymal stem cells in cell proliferation, migration and [Ca(2+)]i kinetics. Moreover, we unexpectedly found that, compared with male ones, female bone marrow-derived mesenchymal stem cells had a higher expression level of glyceraldehyde-3-phosphate dehydrogenase and manipulations of its expression in female or male bone marrow-derived mesenchymal stem cells profoundly affected their cellular behaviours and therapeutic efficacies against pulmonary arterial hypertension.
Our results suggest that glyceraldehyde-3-phosphate dehydrogenase plays a critical role in determining the superior functions of female bone marrow-derived mesenchymal stem cells in cell therapy against pulmonary arterial hypertension by regulating [Ca(2+)]i signal-associated cellular behaviours.
尽管在常规治疗方面取得了重大进展，但肺动脉高压（一种慢性肺部疾病）的预后仍然不容乐观。干细胞疗法代表了一种新颖而有效的治疗方式。本研究旨在深入了解骨髓间充质干细胞在治疗肺动脉高压方面的性别差异及其潜在机制。
通过体内实验，我们首次表明，与雄性骨髓间充质干细胞相比，雌性骨髓间充质干细胞在 C57BL/6J 小鼠的野百合碱诱导的肺动脉高压治疗中具有更好的治疗潜力。体外实验表明，雌性骨髓间充质干细胞在细胞增殖、迁移和[Ca(2+)]i 动力学方面具有更好的功能。此外，我们出人意料地发现，与雄性骨髓间充质干细胞相比，雌性骨髓间充质干细胞的甘油醛-3-磷酸脱氢酶表达水平更高，并且对雌性或雄性骨髓间充质干细胞中甘油醛-3-磷酸脱氢酶的表达进行操作，会显著影响其细胞行为和对肺动脉高压的治疗效果。
我们的研究结果表明，甘油醛-3-磷酸脱氢酶在通过调节[Ca(2+)]i 信号相关的细胞行为来确定雌性骨髓间充质干细胞在细胞治疗肺动脉高压方面的优越功能方面发挥着关键作用。
