Sex dimorphisms in activated mesenchymal stem cell function
Sex dimorphisms in activated mesenchymal stem cell function
复制标题
DOI：
10.1097/01.shk.0000233195.63859.ef
复制
发表时间：
2006-12-01
期刊：
影响因子：
3.1
通讯作者：
Meldrum, Daniel R.
中科院分区：
文献类型：
--
作者：
Crisostomo, Paul R.;Wang, Meijing;Meldrum, Daniel R.
骨髓来源干细胞(BMSCs)的可塑性导致了积极的重塑和活性组织的再生。然而，骨髓间充质干细胞释放限制细胞凋亡和炎症的生长因子，可能在器官保护中发挥重要作用。最近的研究还表明，那些循环中BMSC计数较高的患者可能对败血症和创伤性侮辱更具抵抗力。对这种侮辱的反应存在明显的性别差异。在BMSC群体中，间充质干细胞(MSCs)可能具有临床优势。因此，我们假设MSC对急性损伤的旁分泌反应存在性别差异。-间充质干细胞取自雄性和雌性小鼠。每孔100万个MSCs(每组三个孔)在低氧和增加内毒素(内毒素[LPS])和过氧化氢剂量的情况下进行应激。采用酶联免疫吸附试验检测血管内皮细胞生长因子(VEGF)和肿瘤坏死因子-α(TNF-α)的产生，以检测骨髓间充质干细胞的活性。如果P<；0.05，则认为差异显著。结果：脂多糖对雄性和雌性MSCs均有明显的激活作用。然而，在所有剂量的脂多糖刺激下，雌性MSCs比雄性MSCs产生更多的血管内皮生长因子。低氧1h和氢氧化氢暴露也导致雌性MSCs比雄性MSCs产生更多的血管内皮生长因子。在急性脂多糖和低氧条件下，雌性MSCs表达的肿瘤坏死因子α明显低于雄性MSCs。结论：本研究首次证明激活的MSC功能存在性别差异。祖细胞功能的性别差异可能对理解观察到的宿主对伤害反应的性别差异具有重要意义。
The plasticity of bone marrow-derived stem cells (BMSCs) has resulted in positive remodeling and the regeneration of viable tissues. However, BMSC release of growth factors, which limit apoptosis and inflammation, may play an important role in conferring organ protection. Recent studies also indicate that those patients with higher circulating BMSC counts may be more resistant to septic and traumatic insults. There are clear sex differences in response to such insults. Within the population of BMSC, mesenchymal stem cells (MSCs) may have clinical advantages. Therefore, we hypothesize that sex differences in the MSC paracrine response to acute injury exist. -Mesenchymal stem cells were obtained from male and female mice. One million MSCs per well (triplicate wells per group) were stressed by hypoxia and increasing doses of endotoxin (lipopolysaccharide [LPS]) and hydrogen peroxide. Mesenchymal stem cell activation was determined by measuring vascular endothelial growth factor (VEGF) and tumor necrosis factor alpha production by enzyme-linked immunosorbent assay. Differences were considered significant if P < 0.05. Results-Lipopolysaccharide resulted in significant activation of both male and female MSCs. However, LPS provoked significantly more VEGF production in female MSCs versus male MSCs at all LPS doses. Hypoxia of 1 h and hydrogen pyroxide exposure also caused significantly more VEGF production in female MSCs versus male MSCs. Female MSCs expressed significantly less tumor necrosis factor a than male MSCs after acute LPS and hypoxia. Conclusion-This study constitutes the first demonstration that sex differences exist in activated MSC function. Sex differences in progenitor cell function may have important implications in understanding the observed sex differences in the host's response to injury.