Department of Biomedical Engineering Schulich School of Engineering, University of Calgary, Calgary, Alberta, Canada.
Obesity (Silver Spring). 2014 Mar;22(3):721-9. doi: 10.1002/oby.20580. Epub 2013 Sep 23.
The impact of dietary-induced obesity (DIO) on stem cell engraftment and the respective therapeutic potential of stem cell engraftment in DIO have not been reported. The objectives of this study were to examine the impact of DIO on the survival and efficacy of intravenous bone marrow-derived mesenchymal stem cell (MSC) administration in the conscious C57BL/6 mouse.
Male mice consumed either a chow (CH) or high fat (HF, 60% kcal) diet for 18 weeks and were subsequently treated with MSC over a 6-day period. Key measurements included tissue-specific cell engraftment, glucose and insulin sensitivity, inflammation, and oxidative stress.
MSC administration had no effect on inflammatory markers, glucose, or insulin sensitivity. DIO mice showed increases in MSC engraftment in multiple tissues compared with their CH counterparts. Engraftment was increased in the HF liver where MSC administration attenuated DIO-induced oxidative stress. These liver-specific alterations in HF-MSC were associated with increases in stanniocalcin-1 (STC1) and uncoupling protein 2 (UCP2), which contribute to cell survival and modulate mitochondrial bioenergetics.
Results suggest that MSC administration in DIO promotes engraftment and mitigates hepatic oxidative stress. These data invite further exploration into the therapeutic potential of stem cells for the treatment of DIO oxidative stress in the liver.
饮食诱导肥胖（DIO）对干细胞移植的影响，以及干细胞移植在 DIO 中的治疗潜力尚未得到报道。本研究的目的是研究 DIO 对静脉注射骨髓间充质干细胞（MSC）给药在清醒 C57BL/6 小鼠中存活和疗效的影响。
雄性小鼠分别食用标准饲料（CH）或高脂肪（HF，60%卡路里）饮食 18 周，随后在 6 天内接受 MSC 治疗。关键测量包括组织特异性细胞移植、葡萄糖和胰岛素敏感性、炎症和氧化应激。
MSC 给药对炎症标志物、葡萄糖或胰岛素敏感性没有影响。与 CH 相比，DIO 小鼠的多种组织中 MSC 移植增加。HF 肝脏中的 MSC 移植增加，MSC 给药减轻了 DIO 诱导的氧化应激。HF-MSC 中这些肝脏特异性变化与增加的 STC1 和 UCP2 相关，它们有助于细胞存活并调节线粒体生物能学。
结果表明，DIO 中 MSC 给药促进了移植并减轻了肝氧化应激。这些数据邀请进一步探索干细胞在治疗 DIO 肝脏氧化应激中的治疗潜力。
