Zenovich A G, Panoskaltsis-Mortari A, Caron G J, Kolb A G, Fremming R, Nelson W D, Taylor D A
Center for Cardiovascular Repair, Section of Pediatric Bone Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
Transplant Proc. 2008 Mar;40(2):641-3. doi: 10.1016/j.transproceed.2008.01.040.
There are differences in symptoms, risk stratification, and efficacy of pharmacological treatments between men and women with coronary artery disease (CAD). The results of clinical studies of cell therapy in CAD patients are mixed. The relevance of sex to response to cell therapy is unknown. We investigated sex-based differences in response to bone marrow mononuclear cells (BM-MNCs) in atherosclerotic apoliproprotein E-knockout (ApoE -/-) mice.
Twenty-three male and 27 female ApoE -/- mice fed on a high-fat diet received four intravenous BM-MNC injections (C57BL6/J mice) starting at 14 weeks of age; male or female BM-MNCs were administered. Thirteen male and 20 female atherosclerotic ApoE -/- mice received vehicle. Aortic plaque burden (%), recipient bone marrow progenitor cell profiles (FACS-LSR II, FlowJo) and 22 circulating cytokine panel (LINCOplex) were quantified and analyzed statistically (SSPS, P < or 5).
Quantitative and semiquantitative results are presented. Increased G-CSF levels correlated with plaque reduction (r = -.86, P = .0004). G-CSF was clustered with IL-15.
Female but not male BM-MNCs exhibited atheroprotection in male atherosclerotic ApoE -/- mice. Plaque lesions did not attenuate atherosclerosis in female ApoE -/- mice with BM-MNCs of either donor sex. An increase in regulatory and in Th2-type response may be required for atheroprotection. Sex-based differences in vascular repair have implications for cell therapy trials in CAD.
患有冠状动脉疾病（CAD）的男性和女性在症状、风险分层及药物治疗效果方面存在差异。CAD患者细胞治疗的临床研究结果不一。性别与细胞治疗反应的相关性尚不清楚。我们研究了动脉粥样硬化载脂蛋白E基因敲除（ApoE -/-）小鼠对骨髓单个核细胞（BM-MNCs）反应的性别差异。
23只雄性和27只雌性高脂饮食喂养的ApoE -/-小鼠，从14周龄开始接受4次静脉注射BM-MNCs（C57BL6/J小鼠）；分别给予雄性或雌性BM-MNCs。13只雄性和20只雌性动脉粥样硬化ApoE -/-小鼠接受赋形剂。对主动脉斑块负荷（%）、受体骨髓祖细胞谱（FACS-LSR II，FlowJo）和22种循环细胞因子组（LINCOplex）进行定量并统计分析（SSPS，P<或=0.05）。
给出了定量和半定量结果。G-CSF水平升高与斑块减少相关（r = -0.86，P = 0.0004）。G-CSF与IL-15聚集在一起。
雌性而非雄性BM-MNCs在雄性动脉粥样硬化ApoE -/-小鼠中表现出抗动脉粥样硬化作用。在接受任一供体性别的BM-MNCs的雌性ApoE -/-小鼠中，斑块病变并未减轻动脉粥样硬化。抗动脉粥样硬化保护可能需要调节性反应和Th2型反应增加。血管修复的性别差异对CAD细胞治疗试验具有重要意义。
